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Volume 31,Issue 5,2024 Table of Contents
2024, 31(5):429-436.
DOI: 10.3872/j.issn.1007-385X.2024.05.001
Abstract:
The genesis and progression of cancer is a process of immunoediting that consists of 3 phases, namely elimination,equilibrium and escape phases. This process is also a microevolutionary game process between the body and the tumor. Data from mouse tumors and some human tumors shows that both T cell-based adaptive immunity and innate lymphoid cell (ILC)-based innate immunity participate in cancer immunoediting. The ILCs, which belong to tissue-resident cells and consist of multiple subsets, are a unique branch of the innate immune system discovered over a decade ago. The characteristics and functions of ILCs exhibit significant heterogeneity and are regulated by a variety of factors secreted by various kinds of cells. ILCs participate not only in the regulation of tissue homeostasis and inflammatory responses, but also, through various mechanisms, in the formation of tumor microenvironment and cancer immunoediting process. This paper studies the classification and characteristics of ILCs and their roles and mechanisms in tumors, aiming to explore new thoughts for the pathogenesis, diagnosis and treatment of tumors.
The genesis and progression of cancer is a process of immunoediting that consists of 3 phases, namely elimination,equilibrium and escape phases. This process is also a microevolutionary game process between the body and the tumor. Data from mouse tumors and some human tumors shows that both T cell-based adaptive immunity and innate lymphoid cell (ILC)-based innate immunity participate in cancer immunoediting. The ILCs, which belong to tissue-resident cells and consist of multiple subsets, are a unique branch of the innate immune system discovered over a decade ago. The characteristics and functions of ILCs exhibit significant heterogeneity and are regulated by a variety of factors secreted by various kinds of cells. ILCs participate not only in the regulation of tissue homeostasis and inflammatory responses, but also, through various mechanisms, in the formation of tumor microenvironment and cancer immunoediting process. This paper studies the classification and characteristics of ILCs and their roles and mechanisms in tumors, aiming to explore new thoughts for the pathogenesis, diagnosis and treatment of tumors.
2024, 31(5):437-444.
DOI: 10.3872/j.issn.1007-385X.2024.05.002
Abstract:
Objective: To explore the effect of midchain fatty acid decanoic acid on CD8+ T cell activation and its effect and mechanism in CD8+ T cell-mediated anti-tumor immune response. Methods: Subcutaneous melanoma B16F10 cells tumor-bearing C57BL/6 mouse models were established and randomly divided into the decanoic acid group (10 mg/kg decanoic acid by gavage) and the control group (equal amount of solvent by gavage). The effect of decanoic acid on the growth of mouse tumors and their survival rate were measured. The activation of tumor-infiltrated CD8+ T cells in the tumor microenvironment was detected by flow cytometry. The α-CD8 mAb was used to deplete CD8+ T cells in B16F10 tumor-bearing mice, and the effect on the tumor volume was observed. Mouse primary CD8+ T cells were treated with decanoic acid, and T cell receptor (TCR) activation, effector cytokine production as well as proliferation and metabolism levels were detected by WB, ELISA, qPCR, and flow cytometry. In B16F10 tumor-bearing mouse model, the effects of administration of α-PD-1 mAb combined with decanoic acid on the growth of mouse tumors and mouse survival rate were observed. Results: In the mouse melanoma model, compared with those in the control group the volume of mouse transplanted tumors significantly reduced and mouse survival rate significantly increased in the decanoic acid group. (both P<0.05). The expression levels of IFN-γ and TNF-α in tumor-infiltrating CD8+ T cells were significantly higher in the decanoic acid group than that in the control group (P<0.01). The killing ability of OT-I T cells against B16F10-OVA cells was significantly elevated after treatment with decanoic acid (P<0.01). The suppressive effect of decanoic acid on transplanted tumors was significantly reduced after CD8+ T cells were depleted with α-CD8 mAb in the melanoma mouse model (P<0.000 1). Mouse-derived primary CD8+ T cells treated with decanoic acid showed significantly higher levels of TCR activation, increased production of cytokines IL-2 and IFN-γ, and significantly up-regulated the mitochondrial metabolic level (all P<0.05). In the melanoma mouse model, decanoic acid in combination with α-PD-1 mAb significantly inhibited tumor growth and increased the survival rate (both P<0.05). Conclusion: Decanoic acid can enhance the anti-tumor immune responses by promoting CD8+ T cell activation.
Objective: To explore the effect of midchain fatty acid decanoic acid on CD8+ T cell activation and its effect and mechanism in CD8+ T cell-mediated anti-tumor immune response. Methods: Subcutaneous melanoma B16F10 cells tumor-bearing C57BL/6 mouse models were established and randomly divided into the decanoic acid group (10 mg/kg decanoic acid by gavage) and the control group (equal amount of solvent by gavage). The effect of decanoic acid on the growth of mouse tumors and their survival rate were measured. The activation of tumor-infiltrated CD8+ T cells in the tumor microenvironment was detected by flow cytometry. The α-CD8 mAb was used to deplete CD8+ T cells in B16F10 tumor-bearing mice, and the effect on the tumor volume was observed. Mouse primary CD8+ T cells were treated with decanoic acid, and T cell receptor (TCR) activation, effector cytokine production as well as proliferation and metabolism levels were detected by WB, ELISA, qPCR, and flow cytometry. In B16F10 tumor-bearing mouse model, the effects of administration of α-PD-1 mAb combined with decanoic acid on the growth of mouse tumors and mouse survival rate were observed. Results: In the mouse melanoma model, compared with those in the control group the volume of mouse transplanted tumors significantly reduced and mouse survival rate significantly increased in the decanoic acid group. (both P<0.05). The expression levels of IFN-γ and TNF-α in tumor-infiltrating CD8+ T cells were significantly higher in the decanoic acid group than that in the control group (P<0.01). The killing ability of OT-I T cells against B16F10-OVA cells was significantly elevated after treatment with decanoic acid (P<0.01). The suppressive effect of decanoic acid on transplanted tumors was significantly reduced after CD8+ T cells were depleted with α-CD8 mAb in the melanoma mouse model (P<0.000 1). Mouse-derived primary CD8+ T cells treated with decanoic acid showed significantly higher levels of TCR activation, increased production of cytokines IL-2 and IFN-γ, and significantly up-regulated the mitochondrial metabolic level (all P<0.05). In the melanoma mouse model, decanoic acid in combination with α-PD-1 mAb significantly inhibited tumor growth and increased the survival rate (both P<0.05). Conclusion: Decanoic acid can enhance the anti-tumor immune responses by promoting CD8+ T cell activation.
2024, 31(5):445-451.
DOI: 10.3872/j.issn.1007-385X.2024.05.003
Abstract:
Objective: To investigate the effect of ginsenoside Rb1 (Gn-Rb1) on oxeiptosis in hepatocellular carcinoma (HCC) HepG2 cells and its possible molecular mechanism. Methods: Bioinformatic was used to analyse the effect of the expression of PGAM5, a key gene of oxeiptosis, on the survival time of HCC patients. HCC tissues and paracancerous tissues of 8 HCC patients admitted into Liaoning Provincial Tumor Hospital were selected, and the expressions of oxeiptosis-related gene proteins and mRNAs were detected by WB assay and qPCR. HepG2 cells were randomly divided into the control group and the Gn-Rb1 group (intervened with 200 μmol/L Gn-Rb1). The effects of Gn-Rb1 on the colony formation ability and the migration ability of HepG2 cells were detected by the cell clone formation assay and the cell scratch assay, respectively. ELISA was used to detect the effect on the level of ROS. Microplate was used to detect the effect on the level of LDH; the effects of Gn-Rb1 on the expressions of key gene proteins and mRNAs were detected by WB assay and qPCR. Results: Bioinformatic analysis revealed that, compared with low-expression patients, patients with PGAM5 high-expression hepatocellular carcinoma had longer overall survival time (P<0.05). In clinical hepatocellular carcinoma and paracancerous tissue samples, it was found that compared with paracancerous tissues, at protein and mRNA levels, the expressions of KEAP1 and PGAM5 in tumor tissues were significantly lower; the expression of NRF2 was significantly higher (all P<0.01); and the expression of p-AIFM1 was significantly higher (P<0.05). After HepG2 cells were intervened with 200 μmol/L Gn-Rb1, compared with those in the control group, the migratory and colony-forming abilities of HepG2 cells in the Gn-Rb1 group reduced significantly (all P<0.01), and the level of LDH increased significantly (P<0.05). Compared with the control group, at mRNA and protein levels, the expressions of KEAP1 and PGAM5 in the Gn-Rb1 group were significantly higher (all P<0.05); the expression of NRF2 was significantly lower (all P<0.05); and the expression of p-AIFM1 protein was significantly lower (P<0.01). Conclusion: Oxeiptosis is inhibited in hepatocellular carcinoma tissues, and Gn-Rb1 promotes oxeiptosis in HCC HepG2 cells by regulating the KEAP1/PGAM5/AIFM1 pathway, thus suppressing the proliferation and migration abilities of HepG2 cells.
Objective: To investigate the effect of ginsenoside Rb1 (Gn-Rb1) on oxeiptosis in hepatocellular carcinoma (HCC) HepG2 cells and its possible molecular mechanism. Methods: Bioinformatic was used to analyse the effect of the expression of PGAM5, a key gene of oxeiptosis, on the survival time of HCC patients. HCC tissues and paracancerous tissues of 8 HCC patients admitted into Liaoning Provincial Tumor Hospital were selected, and the expressions of oxeiptosis-related gene proteins and mRNAs were detected by WB assay and qPCR. HepG2 cells were randomly divided into the control group and the Gn-Rb1 group (intervened with 200 μmol/L Gn-Rb1). The effects of Gn-Rb1 on the colony formation ability and the migration ability of HepG2 cells were detected by the cell clone formation assay and the cell scratch assay, respectively. ELISA was used to detect the effect on the level of ROS. Microplate was used to detect the effect on the level of LDH; the effects of Gn-Rb1 on the expressions of key gene proteins and mRNAs were detected by WB assay and qPCR. Results: Bioinformatic analysis revealed that, compared with low-expression patients, patients with PGAM5 high-expression hepatocellular carcinoma had longer overall survival time (P<0.05). In clinical hepatocellular carcinoma and paracancerous tissue samples, it was found that compared with paracancerous tissues, at protein and mRNA levels, the expressions of KEAP1 and PGAM5 in tumor tissues were significantly lower; the expression of NRF2 was significantly higher (all P<0.01); and the expression of p-AIFM1 was significantly higher (P<0.05). After HepG2 cells were intervened with 200 μmol/L Gn-Rb1, compared with those in the control group, the migratory and colony-forming abilities of HepG2 cells in the Gn-Rb1 group reduced significantly (all P<0.01), and the level of LDH increased significantly (P<0.05). Compared with the control group, at mRNA and protein levels, the expressions of KEAP1 and PGAM5 in the Gn-Rb1 group were significantly higher (all P<0.05); the expression of NRF2 was significantly lower (all P<0.05); and the expression of p-AIFM1 protein was significantly lower (P<0.01). Conclusion: Oxeiptosis is inhibited in hepatocellular carcinoma tissues, and Gn-Rb1 promotes oxeiptosis in HCC HepG2 cells by regulating the KEAP1/PGAM5/AIFM1 pathway, thus suppressing the proliferation and migration abilities of HepG2 cells.
2024, 31(5):452-461.
DOI: 10.3872/j.issn.1007-385X.2024.05.004
Abstract:
Objective: To investigate the effects of wild-type vesicular stomatitis virus strain (VSV-IN ) on immunomodulation and tumour metastasis in mouse triple negative breast cancer (TNBC) 4T1 cell transplantation model mice. Methods: After VSV-IN infected 4T1 cells with MOI=1, MOI=10 and MOI=100 for 12, 24 and 48 h, 4T1 cell mortality was detected by CCK-8 method, migration ability by scratch healing assay, and the expressions of E-cadherin, MMP-2 and MMP-9 mRNA by qPCR. The fat pads of female BALB/c mice were inoculated with 0.1 mL of 4T1 cells with a cell density of 1×106 cells/mL to construct a 4T1 cell-loaded mouse model. When the tumour volume reached 200 mm3, the mice were injected intratumorally with PBS, taxol (TAX) (15 mg/kg), and VSV (1×106 pfu) once a week, respectively. After 4 administrations, mice were executed, stripped of intact grafted tumour tissues, and tumour volume and mass were measured. Histopathological sections of the lungs were stained with H-E, and tumour metastatic nodules of the lungs were observed. The proportion of T-cell subpopulations in the spleen was detected by flow cytometry.The levels of serum IL-6 and TNF-α were detected by ELISA. The expression levels of migration-related proteins in mammary gland tumours were analysed by using the online analysis of GEPIA. The expressions of MMP-2, MMP-9 and E-cadherin in mouse tumours were detected by immunohistochemistry, and the affinity of G and M proteins of VSV-IN and ERK2 and E-cadherin was predicted by protein-protein docking technology. Results: The mortality rate of 4T1 cells after 48 hours of VSV treatment at MOI=10 and 100 were significantly higher than that of the control group (P<0.01). Compared with that of the control group, the cell migration rate of the VSV-IN group (MOI=10) was significantly lower (P<0.01), and the relative expression of MMP-9 mRNA was significantly lower (P<0.05).Compared with those in the mice of the control group, transplanted tumours in the mice of the VSV-IN group grew more slowly, and their endpoint volume was significantly reduced (P<0.05). The number of lung metastatic nodules in the mice of the VSV group was significantly less than that of the control group ([12.86±1.86] vs [24±3.67], P<0.01). The proportions of splenic CD4+ T and CD8+ T cells in the VSV group were significantly higher (both P<0.05). The serum TNF-α and IL-6 levels were significantly higher (both P<0.01). GEPIA tool analysis revealed that the expression levels of E-cadherin and MMP-9 were higher in breast cancer tissues than in paracancerous tissues (P<0.05). The expression of MMP-9 in the tumour cells of the mice in the VSV-IN group was significantly lower than that in the control group (P<0.05). The binding free energies of G and M proteins of VSV-IN to ERK2 were -11.7 kcal/mol and -6.4 kcal/mol, respectively. Conclusion: Wild-type VSV-IN inhibits the growth and metastasis of transplanted tumours in 4T1 tumor-bearing mice, which may be related to its promotion of anti-tumour immunity and modulation of the expression of migration-related proteins.
Objective: To investigate the effects of wild-type vesicular stomatitis virus strain (VSV-IN ) on immunomodulation and tumour metastasis in mouse triple negative breast cancer (TNBC) 4T1 cell transplantation model mice. Methods: After VSV-IN infected 4T1 cells with MOI=1, MOI=10 and MOI=100 for 12, 24 and 48 h, 4T1 cell mortality was detected by CCK-8 method, migration ability by scratch healing assay, and the expressions of E-cadherin, MMP-2 and MMP-9 mRNA by qPCR. The fat pads of female BALB/c mice were inoculated with 0.1 mL of 4T1 cells with a cell density of 1×106 cells/mL to construct a 4T1 cell-loaded mouse model. When the tumour volume reached 200 mm3, the mice were injected intratumorally with PBS, taxol (TAX) (15 mg/kg), and VSV (1×106 pfu) once a week, respectively. After 4 administrations, mice were executed, stripped of intact grafted tumour tissues, and tumour volume and mass were measured. Histopathological sections of the lungs were stained with H-E, and tumour metastatic nodules of the lungs were observed. The proportion of T-cell subpopulations in the spleen was detected by flow cytometry.The levels of serum IL-6 and TNF-α were detected by ELISA. The expression levels of migration-related proteins in mammary gland tumours were analysed by using the online analysis of GEPIA. The expressions of MMP-2, MMP-9 and E-cadherin in mouse tumours were detected by immunohistochemistry, and the affinity of G and M proteins of VSV-IN and ERK2 and E-cadherin was predicted by protein-protein docking technology. Results: The mortality rate of 4T1 cells after 48 hours of VSV treatment at MOI=10 and 100 were significantly higher than that of the control group (P<0.01). Compared with that of the control group, the cell migration rate of the VSV-IN group (MOI=10) was significantly lower (P<0.01), and the relative expression of MMP-9 mRNA was significantly lower (P<0.05).Compared with those in the mice of the control group, transplanted tumours in the mice of the VSV-IN group grew more slowly, and their endpoint volume was significantly reduced (P<0.05). The number of lung metastatic nodules in the mice of the VSV group was significantly less than that of the control group ([12.86±1.86] vs [24±3.67], P<0.01). The proportions of splenic CD4+ T and CD8+ T cells in the VSV group were significantly higher (both P<0.05). The serum TNF-α and IL-6 levels were significantly higher (both P<0.01). GEPIA tool analysis revealed that the expression levels of E-cadherin and MMP-9 were higher in breast cancer tissues than in paracancerous tissues (P<0.05). The expression of MMP-9 in the tumour cells of the mice in the VSV-IN group was significantly lower than that in the control group (P<0.05). The binding free energies of G and M proteins of VSV-IN to ERK2 were -11.7 kcal/mol and -6.4 kcal/mol, respectively. Conclusion: Wild-type VSV-IN inhibits the growth and metastasis of transplanted tumours in 4T1 tumor-bearing mice, which may be related to its promotion of anti-tumour immunity and modulation of the expression of migration-related proteins.
2024, 31(5):462-468.
DOI: 10.3872/j.issn.1007-385X.2024.05.005
Abstract:
Objective: To study, through bioinformatics analysis and cellular biology experiments, the effects of keratin 6A (KRT6A)on the diagnosis, prognosis and immune microenvironment of pancreatic ductal adenocarcinoma (PDAC) and biological behaviors of PDAC PANC1 cells, such as proliferation and apoptosis. Methods: The GEPIA platform was used to integrate the data from the TCGA (The Cancer Genome Atlas) and the GTEx (Genotype-Tissue) to analyze the KTRT6A expression in PDCA tissues. CIBERSORT software was then used to analyze the correlation between KRT6A expression and immune cell infiltration in PDCA tissues, and GSEA analysis was used to study the signaling pathway related to KRT6A gene expression. Immunohistochemical analysis was performed on cancer and adjacent tissue samples from 60 PDAC patients preserved in the Department of Pathology of Changhai Hospital to verify the expression of KRT6A in tumor tissues. The expression of KRT6A gene in PANC1 cells was inhibited by interfering with siRNA. The effects of KRT6A on the proliferation and apoptosis of PDAC cells were detected by CCK-8 assay and flow cytometry. Results: Data analysis of the TCGA and the GTEx found that KRT6A was highly expressed in human PDAC tissues and was significantly correlated with poor survival period of patients (P=0.015). CIBERSORT software and GSEA analysis showed that the infiltration of M2-type macrophages in PDCA tissues with high KRT6A expression was increased (P=0.034), and there was a significant correlation between high KRT6A expression and the up-regulation of Wnt pathway (NES: 1.7359272, P<0.05), pentose phosphate pathway (PPP) (NES:1.5613053, P<0.05) and other signaling pathways (P<0.05 or P<0.01). Immunohistochemical results further verified the high expression of KRT6A in PDCA tissues (P<0.001). Proliferation and apoptosis experiments showed that interfering with KRT6A gene could significantly inhibit the proliferation (P<0.05) and apoptosis (P<0.001) of PANC1 cells. Conclusion: KRT6A is highly expressed in human PDAC tissues, and knocking down its expression can inhibit the proliferation and apoptosis of PANC1 cells, and has the potential to be a new target for PDAC diagnosis and prognosis.
Objective: To study, through bioinformatics analysis and cellular biology experiments, the effects of keratin 6A (KRT6A)on the diagnosis, prognosis and immune microenvironment of pancreatic ductal adenocarcinoma (PDAC) and biological behaviors of PDAC PANC1 cells, such as proliferation and apoptosis. Methods: The GEPIA platform was used to integrate the data from the TCGA (The Cancer Genome Atlas) and the GTEx (Genotype-Tissue) to analyze the KTRT6A expression in PDCA tissues. CIBERSORT software was then used to analyze the correlation between KRT6A expression and immune cell infiltration in PDCA tissues, and GSEA analysis was used to study the signaling pathway related to KRT6A gene expression. Immunohistochemical analysis was performed on cancer and adjacent tissue samples from 60 PDAC patients preserved in the Department of Pathology of Changhai Hospital to verify the expression of KRT6A in tumor tissues. The expression of KRT6A gene in PANC1 cells was inhibited by interfering with siRNA. The effects of KRT6A on the proliferation and apoptosis of PDAC cells were detected by CCK-8 assay and flow cytometry. Results: Data analysis of the TCGA and the GTEx found that KRT6A was highly expressed in human PDAC tissues and was significantly correlated with poor survival period of patients (P=0.015). CIBERSORT software and GSEA analysis showed that the infiltration of M2-type macrophages in PDCA tissues with high KRT6A expression was increased (P=0.034), and there was a significant correlation between high KRT6A expression and the up-regulation of Wnt pathway (NES: 1.7359272, P<0.05), pentose phosphate pathway (PPP) (NES:1.5613053, P<0.05) and other signaling pathways (P<0.05 or P<0.01). Immunohistochemical results further verified the high expression of KRT6A in PDCA tissues (P<0.001). Proliferation and apoptosis experiments showed that interfering with KRT6A gene could significantly inhibit the proliferation (P<0.05) and apoptosis (P<0.001) of PANC1 cells. Conclusion: KRT6A is highly expressed in human PDAC tissues, and knocking down its expression can inhibit the proliferation and apoptosis of PANC1 cells, and has the potential to be a new target for PDAC diagnosis and prognosis.
2024, 31(5):469-476.
DOI: 10.3872/j.issn.1007-385X.2024.05.006
Abstract:
Objective: To investigate the effects of berberine (BBR) combined with XAV939 on the migration and apoptosis of osteosarcoma MG-63 cells and its possible mechanisms. Methods: MG-63 cells were cultured, and 20~120 μmol/L of BBR and 5~60 μmol/L of XAV939 were added, respectively. The cytotoxicity of BBR and XAV939 was determined by CCK-8 assay, and the MG-63 cells were randomly divided into the blank control (NC) group, the BBR group, the XAV939 group, and the BBR+XAV939 combined group. The effects of BBR and XAV939 treatment alone or in combination on the migratory ability of MG-63 cells were detected by the scratch healing assay and the Transwell assay. Hoechst 33258 staining, JC-1 staining and Annexin Ⅴ-FITC/PI double staining flow cytometry were used to detect the effects on cell mitochondrial membrane potential and apoptosis. Immunofluorescence was used to datect the expression of BAX protein, WB assay was used to detect the effects on the expression of MMP-2 and BAX in the cells, and qPCR was used to detect the effects on the expression of the MMP-2 gene. Results: BBR and XAV939 inhibited the proliferation of MG-63 cells in a dose-dependent manner, and 30 μmol/L BBR, 7.5 μmol/L XAV939 were selected for subsequent experiments. Compared with the NC group, 24 h after the cells were treated with BBR (30 μmol/L), XAV939 (7.5 μmol/L) and BBR+XAV939 combination, the migration ability of MG-63 cells was significantly reduced; apoptotic cells were significantly increased (all P<0.05); the mitochondrial membrane potential was decreased (P<0.01); the gene expression of MMP-2, and MMP-2, BAX protein levels were all reduced (all P<0.05). In addition, the effect of the combination group was significantly stronger than that of the monotherapy group (P<0.05 or P<0.01). Conclusion: BBR and XAV939 alone or in combination can inhibit the migration and promote the apoptosis of MG-63 cells. The mechanism may be related to the decreased expression of migration-related protein MMP-2 and increased level of apoptosis-related protein BAX.
Objective: To investigate the effects of berberine (BBR) combined with XAV939 on the migration and apoptosis of osteosarcoma MG-63 cells and its possible mechanisms. Methods: MG-63 cells were cultured, and 20~120 μmol/L of BBR and 5~60 μmol/L of XAV939 were added, respectively. The cytotoxicity of BBR and XAV939 was determined by CCK-8 assay, and the MG-63 cells were randomly divided into the blank control (NC) group, the BBR group, the XAV939 group, and the BBR+XAV939 combined group. The effects of BBR and XAV939 treatment alone or in combination on the migratory ability of MG-63 cells were detected by the scratch healing assay and the Transwell assay. Hoechst 33258 staining, JC-1 staining and Annexin Ⅴ-FITC/PI double staining flow cytometry were used to detect the effects on cell mitochondrial membrane potential and apoptosis. Immunofluorescence was used to datect the expression of BAX protein, WB assay was used to detect the effects on the expression of MMP-2 and BAX in the cells, and qPCR was used to detect the effects on the expression of the MMP-2 gene. Results: BBR and XAV939 inhibited the proliferation of MG-63 cells in a dose-dependent manner, and 30 μmol/L BBR, 7.5 μmol/L XAV939 were selected for subsequent experiments. Compared with the NC group, 24 h after the cells were treated with BBR (30 μmol/L), XAV939 (7.5 μmol/L) and BBR+XAV939 combination, the migration ability of MG-63 cells was significantly reduced; apoptotic cells were significantly increased (all P<0.05); the mitochondrial membrane potential was decreased (P<0.01); the gene expression of MMP-2, and MMP-2, BAX protein levels were all reduced (all P<0.05). In addition, the effect of the combination group was significantly stronger than that of the monotherapy group (P<0.05 or P<0.01). Conclusion: BBR and XAV939 alone or in combination can inhibit the migration and promote the apoptosis of MG-63 cells. The mechanism may be related to the decreased expression of migration-related protein MMP-2 and increased level of apoptosis-related protein BAX.
2024, 31(5):477-483.
DOI: 10.3872/j.issn.1007-385X.2024.05.007
Abstract:
Objective: To explore the effects of kinesin-13 family member 2C (KIF2C) on hepatocellular carcinoma (HCC) cell proliferation, invasion and migration as well as human umbilical vein endothelial cell (HUVEC) angiogenesis to provide potential targets for HCC treatment. Methods: Database data were used to analyze the expression of KIF2C mRNA and protein in HCC tissues and its correlation with the expression of angiogenesis-associated factors (VEGFR2 and HIF-1α). Human normal hepatocytes QSG-7701, HUVEC, and HCC cells Huh-7 and Hep3B2.1-7 were routinely cultured, and sh-NC and sh KIF2C were transfected into Huh-7 and Hep3B2.1-7 cells with Lipofectamine 3000 transfection reagent. qPCR was performed to detect the expression of KIF2C mRNA in QSG-7701, Huh-7 and Hep3B2.1-7 cells of each group, and WB was performed to detect the expression of KIF2C protein in cells of each group, and the effect of KIF2C knockdown on the clone formation of Huh3B2.1-7 and Huh-7 cells was examined in the clonogenic assay. Tubulogenesis assay to detect the effect of conditioned cultures of knockdown KIF2C-expressing Huh-7 and Hep3B2.1-7 cells on the angiogenic capacity of HUVEC cells. Results: Database analysis showed that KIF2C mRNA and protein were highly expressed in HCC tissues (both P<0.01). In addition, database analysis suggested that KIF2C mRNA may also be highly expressed in HCC cells, and the results of KIF2C mRNA and protein expression detected by qPCR and WB showed that its mRNA and protein were highly expressed in HCC cells (both P<0.01) , consistent with the database data analysis. Database data analysis also showed that KIF2C was positively correlated with the expression levels of VEGFR2 and HIF-1α in HCC tissues (P<0.05 or P<0.01). Stable low KIF2C-expressing Huh-7 and Hep3B2.1-7 cells were successfully constructed (both P<0.01), and knockdown of KIF2C expression significantly inhibited the proliferative (all P<0.01), invasive and migratory (all P<0.01) capacities of Huh-7 and Hep3B2.1-7 cells, and the conditioned culture medium of HCC cells with knockdown of KIF2C expression could significantly inhibit the angiogenic capacity of HUVEC cells in vitro (P<0.05 or P<0.01). Conclusion: KIF2C promotes the ability of Huh-7 and Hep3B2.1-7 cells to proliferate, invade and migrate as well as HUVEC angiogenesis, suggesting that KIF2C may be a potential target for the treatment of HCC.
Objective: To explore the effects of kinesin-13 family member 2C (KIF2C) on hepatocellular carcinoma (HCC) cell proliferation, invasion and migration as well as human umbilical vein endothelial cell (HUVEC) angiogenesis to provide potential targets for HCC treatment. Methods: Database data were used to analyze the expression of KIF2C mRNA and protein in HCC tissues and its correlation with the expression of angiogenesis-associated factors (VEGFR2 and HIF-1α). Human normal hepatocytes QSG-7701, HUVEC, and HCC cells Huh-7 and Hep3B2.1-7 were routinely cultured, and sh-NC and sh KIF2C were transfected into Huh-7 and Hep3B2.1-7 cells with Lipofectamine 3000 transfection reagent. qPCR was performed to detect the expression of KIF2C mRNA in QSG-7701, Huh-7 and Hep3B2.1-7 cells of each group, and WB was performed to detect the expression of KIF2C protein in cells of each group, and the effect of KIF2C knockdown on the clone formation of Huh3B2.1-7 and Huh-7 cells was examined in the clonogenic assay. Tubulogenesis assay to detect the effect of conditioned cultures of knockdown KIF2C-expressing Huh-7 and Hep3B2.1-7 cells on the angiogenic capacity of HUVEC cells. Results: Database analysis showed that KIF2C mRNA and protein were highly expressed in HCC tissues (both P<0.01). In addition, database analysis suggested that KIF2C mRNA may also be highly expressed in HCC cells, and the results of KIF2C mRNA and protein expression detected by qPCR and WB showed that its mRNA and protein were highly expressed in HCC cells (both P<0.01) , consistent with the database data analysis. Database data analysis also showed that KIF2C was positively correlated with the expression levels of VEGFR2 and HIF-1α in HCC tissues (P<0.05 or P<0.01). Stable low KIF2C-expressing Huh-7 and Hep3B2.1-7 cells were successfully constructed (both P<0.01), and knockdown of KIF2C expression significantly inhibited the proliferative (all P<0.01), invasive and migratory (all P<0.01) capacities of Huh-7 and Hep3B2.1-7 cells, and the conditioned culture medium of HCC cells with knockdown of KIF2C expression could significantly inhibit the angiogenic capacity of HUVEC cells in vitro (P<0.05 or P<0.01). Conclusion: KIF2C promotes the ability of Huh-7 and Hep3B2.1-7 cells to proliferate, invade and migrate as well as HUVEC angiogenesis, suggesting that KIF2C may be a potential target for the treatment of HCC.
2024, 31(5):484-492.
DOI: 10.3872/j.issn.1007-385X.2024.05.008
Abstract:
Objective: To explore the efficacy and safety of PD-1 antibody versus high-dose interferon in the adjuvant treatment of stage ⅡB-ⅢD melanoma patients after surgery. Methods: Clinical data of patients with stage ⅡB-ⅢD cutaneous and acral melanoma admitted into Nanjing Drum Tower Hospital, the affiliated hospital of Nanjing University Medical School between September 2013 and September 2022 were retrospectively collected. All patients received high-dose interferon (HDI) or PD-1 antibody as adjuvant therapy after surgery. Univariate survival analysis was performed and survival curves were plotted by the Kaplan-Meier method; Log-Rank method was used to analyze and assess whether the differences in RFS, DMFS, and OS between the groups were statistically significant, and prognostic factors were evaluated by univariate and multivariate Cox regression. Results: A total of 91 patients were enrolled in this study with a median follow-up of 31.0 months. The median RFS was 29.2 and 32.3 months in the HDI group and the PD-1 antibody group, respectively, and the difference was not statistically significant (HR=0.90, 95%CI [0.50, 1.64]; P=0.736). The median DMFS and the median OS in the HDI group were 36.0 and 109.2 months respectively, and neither was reached in the PD-1 antibody group (both P>0.05). The most common site of first distant metastasis in both groups was the lung, and there was no statistically significant difference in the incidence of distant metastasis at any site (P>0.05). By univariate Cox analysis, compared with PD-1, antibody HDI reduced the risk of distant metastasis in patients with BRAFV600E/K mutations (HR=10.03, 95% CI [1.10, 91.35]; P=0.041). Subgroup analyses showed that in patients with cutaneous and acral melanoma, the difference in RFS between the HDI group and the PD-1 antibody group was not statistically significant (both P>0.05). The incidence of adverse reactions in the HDI group and the PD-1 antibody group was 83.3% and 79.1%, respectively, most of which were grade 1 or 2. No deaths related to adverse reactions occurred in both groups. Conclusion: In this study, there was no statistically significant difference in clinical efficacy and safety between PD-1 antibody and HDI adjuvant therapy for malignant melanoma patients. Patients with BRAFV600E/K mutations may benefit more from HDI. Numerous prospective studies are needed to further explore the optimal adjuvant treatment options for melanoma patients in Asian populations.
Objective: To explore the efficacy and safety of PD-1 antibody versus high-dose interferon in the adjuvant treatment of stage ⅡB-ⅢD melanoma patients after surgery. Methods: Clinical data of patients with stage ⅡB-ⅢD cutaneous and acral melanoma admitted into Nanjing Drum Tower Hospital, the affiliated hospital of Nanjing University Medical School between September 2013 and September 2022 were retrospectively collected. All patients received high-dose interferon (HDI) or PD-1 antibody as adjuvant therapy after surgery. Univariate survival analysis was performed and survival curves were plotted by the Kaplan-Meier method; Log-Rank method was used to analyze and assess whether the differences in RFS, DMFS, and OS between the groups were statistically significant, and prognostic factors were evaluated by univariate and multivariate Cox regression. Results: A total of 91 patients were enrolled in this study with a median follow-up of 31.0 months. The median RFS was 29.2 and 32.3 months in the HDI group and the PD-1 antibody group, respectively, and the difference was not statistically significant (HR=0.90, 95%CI [0.50, 1.64]; P=0.736). The median DMFS and the median OS in the HDI group were 36.0 and 109.2 months respectively, and neither was reached in the PD-1 antibody group (both P>0.05). The most common site of first distant metastasis in both groups was the lung, and there was no statistically significant difference in the incidence of distant metastasis at any site (P>0.05). By univariate Cox analysis, compared with PD-1, antibody HDI reduced the risk of distant metastasis in patients with BRAFV600E/K mutations (HR=10.03, 95% CI [1.10, 91.35]; P=0.041). Subgroup analyses showed that in patients with cutaneous and acral melanoma, the difference in RFS between the HDI group and the PD-1 antibody group was not statistically significant (both P>0.05). The incidence of adverse reactions in the HDI group and the PD-1 antibody group was 83.3% and 79.1%, respectively, most of which were grade 1 or 2. No deaths related to adverse reactions occurred in both groups. Conclusion: In this study, there was no statistically significant difference in clinical efficacy and safety between PD-1 antibody and HDI adjuvant therapy for malignant melanoma patients. Patients with BRAFV600E/K mutations may benefit more from HDI. Numerous prospective studies are needed to further explore the optimal adjuvant treatment options for melanoma patients in Asian populations.
2024, 31(5):493-500.
DOI: 10.3872/j.issn.1007-385X.2024.05.009
Abstract:
Objective:To engineer a BCMA mutant resistant to γ-secretase cleavage in order to stabilize wild-type BCMA expression after γ-secretase cleavage and to generate target cells for measuring BCMA CAR-T cell cytotoxicity. Methods: Our study aimed to engineer a mutant BCMA protein (BCMA-CD8α TM) that could resist γ-secretase cleavage by replacing the transmembrane domain of the wild-type BCMA protein with the human CD8α sequence. Four different types of cells in which this mutant gene was expressed excessively were engineered, including U266 (U266BCMA Mut), K562 (K562BCMA Mut), SKOV3 (SKOV3BCMA Mut), and CHO (CHOBCMA Mut)cells. BCMA CAR Jurkat cells, loaded with the NFAT-EGFP reporter gene (BCMA-CAR-Jurkat-Reporter), were engineered and co- cultured with U266BCMA Mut cells. The expression level of EGFP was detected by FCM in order to indicate the activation level of NFAT.The cytotoxicity of BCMA CAR-T cells against Luciferase-labeled K562BCMA Mut cells was detected by the luciferase assay. Additionally,real-time cell analysis (RTCA) technique was employed to detect the cytotoxicity of BCMA CAR-T cells against SKOV3BCMA Mut and CHOBCMA Mut cells. Results: Application of γ -secretase inhibitor LY411575 to inhibit γ -secretase activity significantly enhanced the expression level of BCMA on the surface of wild-type U266 cells, and the average fluorescence intensity was increased by more than 10 times. However, the expression level of BCMA gradually decreased after removal of inhibitors (P<0.01). BCMA-CD8α TM mutant could resist the cleavage of γ -secretase and expressed stably on the surface of U266 cells (P>0.05). U266 cells and U266 cells overexpressing BCMA-CD8α TM were co-incubated with BCMA-CAR-Jurkat-Reporter cells, both of which could activate the Reporter system and enhance the expression of EGFP, but the effect was more significant in U266 cells overexpressing BCMA-CD8α TM (P<0.01). BCMA-CD8α TM mutants were successfully overexpressed in 3 BCMA-negative target cells, namely K562, SKOV3 and CHO cells, and the expression level of the mutant was only slightly increased under LY411575 treatment. Luciferase assay results showed that under different target-effect ratios BCMA CAR-T cells could all be specific and efficient in killing K562 cells overexpressing BCMA-CD8α TM. RTCA results showed that under different target ratios BCMA CAR-T cells could all effectively recognize and kill SKOV3 and CHO cells overexpressing BCMA-CD8α TM, but Mock-T cells with the same target ratio had no such effect. Conclusion: The BCMA-CD8α TM mutant engineered in this study can resist γ-secretase cleavage and exhibits stable surface expression on various target cells, thus offering various methods for evaluating the efficacy and specificity of BCMA CAR-T cell cytotoxicity in vitro.
Objective:To engineer a BCMA mutant resistant to γ-secretase cleavage in order to stabilize wild-type BCMA expression after γ-secretase cleavage and to generate target cells for measuring BCMA CAR-T cell cytotoxicity. Methods: Our study aimed to engineer a mutant BCMA protein (BCMA-CD8α TM) that could resist γ-secretase cleavage by replacing the transmembrane domain of the wild-type BCMA protein with the human CD8α sequence. Four different types of cells in which this mutant gene was expressed excessively were engineered, including U266 (U266BCMA Mut), K562 (K562BCMA Mut), SKOV3 (SKOV3BCMA Mut), and CHO (CHOBCMA Mut)cells. BCMA CAR Jurkat cells, loaded with the NFAT-EGFP reporter gene (BCMA-CAR-Jurkat-Reporter), were engineered and co- cultured with U266BCMA Mut cells. The expression level of EGFP was detected by FCM in order to indicate the activation level of NFAT.The cytotoxicity of BCMA CAR-T cells against Luciferase-labeled K562BCMA Mut cells was detected by the luciferase assay. Additionally,real-time cell analysis (RTCA) technique was employed to detect the cytotoxicity of BCMA CAR-T cells against SKOV3BCMA Mut and CHOBCMA Mut cells. Results: Application of γ -secretase inhibitor LY411575 to inhibit γ -secretase activity significantly enhanced the expression level of BCMA on the surface of wild-type U266 cells, and the average fluorescence intensity was increased by more than 10 times. However, the expression level of BCMA gradually decreased after removal of inhibitors (P<0.01). BCMA-CD8α TM mutant could resist the cleavage of γ -secretase and expressed stably on the surface of U266 cells (P>0.05). U266 cells and U266 cells overexpressing BCMA-CD8α TM were co-incubated with BCMA-CAR-Jurkat-Reporter cells, both of which could activate the Reporter system and enhance the expression of EGFP, but the effect was more significant in U266 cells overexpressing BCMA-CD8α TM (P<0.01). BCMA-CD8α TM mutants were successfully overexpressed in 3 BCMA-negative target cells, namely K562, SKOV3 and CHO cells, and the expression level of the mutant was only slightly increased under LY411575 treatment. Luciferase assay results showed that under different target-effect ratios BCMA CAR-T cells could all be specific and efficient in killing K562 cells overexpressing BCMA-CD8α TM. RTCA results showed that under different target ratios BCMA CAR-T cells could all effectively recognize and kill SKOV3 and CHO cells overexpressing BCMA-CD8α TM, but Mock-T cells with the same target ratio had no such effect. Conclusion: The BCMA-CD8α TM mutant engineered in this study can resist γ-secretase cleavage and exhibits stable surface expression on various target cells, thus offering various methods for evaluating the efficacy and specificity of BCMA CAR-T cell cytotoxicity in vitro.
2024, 31(5):501-506.
DOI: 10.3872/j.issn.1007-385X.2024.05.010
Abstract:
嗜酸性粒细胞（Eos）是一种多功能免疫细胞，在外周血循环和组织中均有分布，主要受IL-5和IL-33所诱导产生。Eos 与肺癌在内的多种肿瘤存在相互作用，能够通过直接杀伤、免疫调节、促进肿瘤血管正常化等方式发挥抗肿瘤作用，其功能受诱导的细胞因子、所处的肿瘤微环境（TME）、肿瘤的病理类型、作用的时间不同而具有较强的可塑性。免疫检测点抑制剂（ICI）作为一种新兴免疫疗法极大改变了肺癌的治疗模式，然而，目前在临床实践中，仍然缺乏能够较为稳定且有效地预测其疗效和免疫相关不良反应的生物标志物。相较于PD-L1表达水平、肿瘤突变负荷等生物标志物，Eos 作为一种常见的循环血细胞具有检测成本低、易获取等优点。有多项研究发现，Eos 在肺癌免疫治疗中的特殊改变，且与患者预后和不良反应有一定的相关性。进一步深入开展相关的机制和临床研究后，Eos将具有成为肺癌免疫治疗中有效生物标志物的能力。
嗜酸性粒细胞（Eos）是一种多功能免疫细胞，在外周血循环和组织中均有分布，主要受IL-5和IL-33所诱导产生。Eos 与肺癌在内的多种肿瘤存在相互作用，能够通过直接杀伤、免疫调节、促进肿瘤血管正常化等方式发挥抗肿瘤作用，其功能受诱导的细胞因子、所处的肿瘤微环境（TME）、肿瘤的病理类型、作用的时间不同而具有较强的可塑性。免疫检测点抑制剂（ICI）作为一种新兴免疫疗法极大改变了肺癌的治疗模式，然而，目前在临床实践中，仍然缺乏能够较为稳定且有效地预测其疗效和免疫相关不良反应的生物标志物。相较于PD-L1表达水平、肿瘤突变负荷等生物标志物，Eos 作为一种常见的循环血细胞具有检测成本低、易获取等优点。有多项研究发现，Eos 在肺癌免疫治疗中的特殊改变，且与患者预后和不良反应有一定的相关性。进一步深入开展相关的机制和临床研究后，Eos将具有成为肺癌免疫治疗中有效生物标志物的能力。
2024, 31(5):507-513.
DOI: 10.3872/j.issn.1007-385X.2024.05.011
Abstract:
中性粒细胞作为机体的重要免疫细胞，在感染、自身免疫性疾病等多种炎症反应中发挥重要作用。然而，中性粒细胞在肿瘤的发生发展过程中也扮演重要角色。一方面，中性粒细胞能够通过杀伤肿瘤细胞发挥抗肿瘤作用；另一方面，中性粒细胞也可以通过分泌多种细胞因子或与其他类型细胞相互作用来促进肿瘤细胞发生免疫逃逸。由于中性粒细胞能够通过多种机制来促进肿瘤的发生发展，因此靶向中性粒细胞的免疫治疗也成为了肿瘤免疫治疗的一个新的思路。本文通过介绍中性粒细胞在肿瘤演进过程中发挥的抗肿瘤效应，促进肿瘤免疫逃逸以及中性粒细胞相关的免疫治疗等方面来阐述中性粒细胞在肿瘤发生发展以及免疫治疗中的重要性。
中性粒细胞作为机体的重要免疫细胞，在感染、自身免疫性疾病等多种炎症反应中发挥重要作用。然而，中性粒细胞在肿瘤的发生发展过程中也扮演重要角色。一方面，中性粒细胞能够通过杀伤肿瘤细胞发挥抗肿瘤作用；另一方面，中性粒细胞也可以通过分泌多种细胞因子或与其他类型细胞相互作用来促进肿瘤细胞发生免疫逃逸。由于中性粒细胞能够通过多种机制来促进肿瘤的发生发展，因此靶向中性粒细胞的免疫治疗也成为了肿瘤免疫治疗的一个新的思路。本文通过介绍中性粒细胞在肿瘤演进过程中发挥的抗肿瘤效应，促进肿瘤免疫逃逸以及中性粒细胞相关的免疫治疗等方面来阐述中性粒细胞在肿瘤发生发展以及免疫治疗中的重要性。
2024, 31(5):514-518.
DOI: 10.3872/j.issn.1007-385X.2024.05.012
Abstract:
脂氧合酶（LOX）家族蛋白在恶性肿瘤演进中发挥重要作用，其亚型5-LOX 在多种肿瘤组织和细胞中呈高表达，且与淋巴结转移、患者的生存期有关，可通过诱导Src 的磷酸化、选择性抑制p53 依赖的促凋亡基因转录、促进肿瘤血管形成、刺激上皮-间质转化、形成转移前微环境等，促进肿瘤细胞增殖和转移、抑制凋亡，参与调控肿瘤的恶性演进过程。基于5-LOX及其激活蛋白ALOX5AP的促癌作用，已开发出直接、间接两类抑制剂及COX-2/5-LOX 双重抑制剂，有望通过降低5-LOX 活性或阻断5-LOX代谢途径发挥抗肿瘤作用。本文概述5-LOX在肿瘤中的调控作用以及5-LOX和其激活蛋白抑制剂的研究现状，以期为后续抗肿瘤药物的开发及临床应用提供参考及新的理论依据。
脂氧合酶（LOX）家族蛋白在恶性肿瘤演进中发挥重要作用，其亚型5-LOX 在多种肿瘤组织和细胞中呈高表达，且与淋巴结转移、患者的生存期有关，可通过诱导Src 的磷酸化、选择性抑制p53 依赖的促凋亡基因转录、促进肿瘤血管形成、刺激上皮-间质转化、形成转移前微环境等，促进肿瘤细胞增殖和转移、抑制凋亡，参与调控肿瘤的恶性演进过程。基于5-LOX及其激活蛋白ALOX5AP的促癌作用，已开发出直接、间接两类抑制剂及COX-2/5-LOX 双重抑制剂，有望通过降低5-LOX 活性或阻断5-LOX代谢途径发挥抗肿瘤作用。本文概述5-LOX在肿瘤中的调控作用以及5-LOX和其激活蛋白抑制剂的研究现状，以期为后续抗肿瘤药物的开发及临床应用提供参考及新的理论依据。
2024, 31(5):519-527.
DOI: 10.3872/j.issn.1007-385X.2024.05.013
Abstract:
CRISPR/Cas9基因编辑技术通过精准定位和修改基因序列，可以识别与细胞增殖、迁移、侵袭和化疗耐药性相关的基因，不仅为理解肿瘤发生发展的分子机制奠定了基础，还为实现肿瘤的精准治疗提供了一种方便、高效的方法。由于其具有低成本、高效率的优点，被广泛地应用于精准肿瘤学的基础和临床研究当中，包括用于探寻抗肿瘤药物耐药靶点、筛查驱动基因、优化CAR-T和TCR-T细胞，以及筛选肿瘤靶向基因等。目前，已开展了十余项项使用CRISPR/Cas9技术治疗肿瘤的临床试验，策略多为利用CRISPR/Cas9技术敲除T细胞中的免疫检查点基因后回输患者，以达到免疫激活的效果，大多数研究仍处于Ⅰ期和Ⅱ期阶段。管CRISPR/Cas9基因编辑技术在肿瘤研究与治疗领域展现出了巨大潜力，但仍需面对脱靶效应，以及永久编辑可能带来的弊端等瓶颈，其实际临床效用仍有待更多的深入研究和大规模临床试验的严格验证。
CRISPR/Cas9基因编辑技术通过精准定位和修改基因序列，可以识别与细胞增殖、迁移、侵袭和化疗耐药性相关的基因，不仅为理解肿瘤发生发展的分子机制奠定了基础，还为实现肿瘤的精准治疗提供了一种方便、高效的方法。由于其具有低成本、高效率的优点，被广泛地应用于精准肿瘤学的基础和临床研究当中，包括用于探寻抗肿瘤药物耐药靶点、筛查驱动基因、优化CAR-T和TCR-T细胞，以及筛选肿瘤靶向基因等。目前，已开展了十余项项使用CRISPR/Cas9技术治疗肿瘤的临床试验，策略多为利用CRISPR/Cas9技术敲除T细胞中的免疫检查点基因后回输患者，以达到免疫激活的效果，大多数研究仍处于Ⅰ期和Ⅱ期阶段。管CRISPR/Cas9基因编辑技术在肿瘤研究与治疗领域展现出了巨大潜力，但仍需面对脱靶效应，以及永久编辑可能带来的弊端等瓶颈，其实际临床效用仍有待更多的深入研究和大规模临床试验的严格验证。
2024, 31(5):528-534.
DOI: 10.3872/j.issn.1007-385X.2024.05.014
Abstract:
地舒单抗联合免疫检查点抑制剂在临床治疗骨转移的非小细胞肺癌中取得了良好的治疗效果，其可能通过影响TME、调节T细胞功能、打破中央耐受以及直接作用于RANKL表达的免疫细胞等多种途径来增强抗肿瘤免疫应答。基于一系列临床研究的探索证明其联合治疗可以明显增加患者的无症状生存期和总生存期，提高患者的生存质量。目前联合疗法已经写入肺癌骨转移的指南用药。但现研究仍存在用药机制不明，缺少大型随机对照研究的数据支持及联合用药的用法指南，以及安全性、实用性评估等问题。本文综述了相关研究进展，为出现骨转移的非小细胞肺癌的治疗提供参考。
地舒单抗联合免疫检查点抑制剂在临床治疗骨转移的非小细胞肺癌中取得了良好的治疗效果，其可能通过影响TME、调节T细胞功能、打破中央耐受以及直接作用于RANKL表达的免疫细胞等多种途径来增强抗肿瘤免疫应答。基于一系列临床研究的探索证明其联合治疗可以明显增加患者的无症状生存期和总生存期，提高患者的生存质量。目前联合疗法已经写入肺癌骨转移的指南用药。但现研究仍存在用药机制不明，缺少大型随机对照研究的数据支持及联合用药的用法指南，以及安全性、实用性评估等问题。本文综述了相关研究进展，为出现骨转移的非小细胞肺癌的治疗提供参考。
2024, 31(5):535-537.
DOI: 10.3872/j.issn.1007-385X.2024.05.015
Abstract:
免疫治疗是高危神经母细胞瘤（HR-NB）治疗方案中的重要组成部分，那西妥单抗是一种靶向双唾液酸神经节苷脂（GD2）的人源化单克隆抗体，通过与肿瘤细胞表面的GD2抗原结合，引发抗体介导的细胞毒性反应并激活免疫系统中的补体系统，从而达到杀死肿瘤细胞的目的。然而那西妥单抗输注过程中不良事件发生率较高。本文报道了1例HR-NB患儿输注那西妥单抗时突发过敏性休克的病例，同时对那西妥单抗不良反应种类及过敏发生机制进行了深入分析，以期为HR-NB患儿那西妥单抗的输注方案和全程管理提供可参考的意见。
免疫治疗是高危神经母细胞瘤（HR-NB）治疗方案中的重要组成部分，那西妥单抗是一种靶向双唾液酸神经节苷脂（GD2）的人源化单克隆抗体，通过与肿瘤细胞表面的GD2抗原结合，引发抗体介导的细胞毒性反应并激活免疫系统中的补体系统，从而达到杀死肿瘤细胞的目的。然而那西妥单抗输注过程中不良事件发生率较高。本文报道了1例HR-NB患儿输注那西妥单抗时突发过敏性休克的病例，同时对那西妥单抗不良反应种类及过敏发生机制进行了深入分析，以期为HR-NB患儿那西妥单抗的输注方案和全程管理提供可参考的意见。
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- 《中国肿瘤生物治疗杂志》
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- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
- 邮编：200433
- 电话：021-81871002-22
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.