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Volume 30,Issue 1,2023 Table of Contents
2023, 30(1):1-9.
DOI: 10.3872/j.issn.1007-385X.2023.01.001
Abstract:
RNA-binding protein (RBP), due to its unique biological functions, has become one of the favorite screening targets for tumor biotherapy, which is likely to bring new opportunities for tumor biotherapy. RBP can regulate the DNA-RNA-protein interaction network in tumor cells, tumor microenvironment immune cells and interstitial cells, and thus widely affecting tumor occurrence and development, anti-tumor immune response and tumor immune evasion. Nowadays, the research of RBP-related tumor biotherapy mainly focuses on therapeutic vaccines, immune cell therapy and epigenetic modulation therapy etc., and some of the research advances have been applied into the clinical trial. With the development of new theories and technologies and the innovation of research models,RBP-targeted therapy has been gradually getting rid of the dilemma of difficult target and poor efficacy, and ushering in new opportunities. New strategies such as improving precise targeting and optimizing drug combinations have injected new vitality into tumor biotherapy, which is of great significance to the development of personalized medicine.
RNA-binding protein (RBP), due to its unique biological functions, has become one of the favorite screening targets for tumor biotherapy, which is likely to bring new opportunities for tumor biotherapy. RBP can regulate the DNA-RNA-protein interaction network in tumor cells, tumor microenvironment immune cells and interstitial cells, and thus widely affecting tumor occurrence and development, anti-tumor immune response and tumor immune evasion. Nowadays, the research of RBP-related tumor biotherapy mainly focuses on therapeutic vaccines, immune cell therapy and epigenetic modulation therapy etc., and some of the research advances have been applied into the clinical trial. With the development of new theories and technologies and the innovation of research models,RBP-targeted therapy has been gradually getting rid of the dilemma of difficult target and poor efficacy, and ushering in new opportunities. New strategies such as improving precise targeting and optimizing drug combinations have injected new vitality into tumor biotherapy, which is of great significance to the development of personalized medicine.
2023, 30(1):10-19.
DOI: 10.3872/j.issn.1007-385X.2023.01.002
Abstract:
Platelets are considered as important participants in the process of tumorigenesis and tumor development, which can directly or indirectly affect the growth and metastasis of tumors by constructing an inflammatory microenvironment, promoting angiogenesis and mediating tumor immune escape. As the tumor microenvironment dynamically changes, the number, volume, and molomics of platelets change accordingly, suggesting that platelet-related biomarkers have great potential to reflect tumor load evolution. Based on the promoting effect of platelets on the process of tumorigenesis and tumor development, platelets are considered as important targets for tumor biotherapy. Targeted inhibition of platelet function can significantly control tumor progression and improve patient outcomes. In addition, platelets have a strong affinity for tumor tissues. Constructing targeted anti-tumor agents with the idea of platelet-targeting or platelet-mimicking can effectively increase the affinity towards tumor tissues and the biocompatibility of nanodrugs, which is an emerging strategy to improve the efficiency of targeted therapy. This paper focuses on the complex interactions between platelets and tumors, summarizing the mechanisms of action and highlighting platelet-related tumor markers and anti-tumor targeted therapies.
Platelets are considered as important participants in the process of tumorigenesis and tumor development, which can directly or indirectly affect the growth and metastasis of tumors by constructing an inflammatory microenvironment, promoting angiogenesis and mediating tumor immune escape. As the tumor microenvironment dynamically changes, the number, volume, and molomics of platelets change accordingly, suggesting that platelet-related biomarkers have great potential to reflect tumor load evolution. Based on the promoting effect of platelets on the process of tumorigenesis and tumor development, platelets are considered as important targets for tumor biotherapy. Targeted inhibition of platelet function can significantly control tumor progression and improve patient outcomes. In addition, platelets have a strong affinity for tumor tissues. Constructing targeted anti-tumor agents with the idea of platelet-targeting or platelet-mimicking can effectively increase the affinity towards tumor tissues and the biocompatibility of nanodrugs, which is an emerging strategy to improve the efficiency of targeted therapy. This paper focuses on the complex interactions between platelets and tumors, summarizing the mechanisms of action and highlighting platelet-related tumor markers and anti-tumor targeted therapies.
2023, 30(1):20-27.
DOI: 10.3872/j.issn.1007-385X.2023.01.003
Abstract:
Objective: To investigate the effect of interfering the expression of four and a half LIM-only protein 2 (FHL2) on the expression of O6-methylguanine DNA methyltransferase (MGMT) and temozolomide (TMZ) resistance of glioblastoma U87 cells.Methods: Lentiviruses carrying different sequences of FHL2 interference sequences (shFHL2-1#, shFHL2-4#) and negative control (shN) were infected into U87 cells, namely shFHL2-1# group, shFHL2-4# group, and shN group, respectively. siMGMT-1#, siMGMT-4#,and siN were transfected into U87 cells by siRNA transfection technology, namely siMGMT-1# group, siMGMT-4# group, and siN group, respectively. The FHL2 or MGMT knockdown efficiency was verified by qPCR and WB. The above groups of cells were treated with TMZ (the DMSO treatment group was used as the control), and then the proliferation of cells with FHL2 or MGMT knockdown before and after TMZ treatment was detected by CCK-8 method and cell clone formation assay, the apoptosis of cells in FHL2 knockdown group before and after TMZ treatment was detected by flow cytometry. WB method and immunofluorescence method was used to detect the effect of FHL2 knockdown on the expression of MGMT in U87 cells. WB method was used to detect the effect of TMZ treatment on the expression levels of FHL2 and MGMT in each group of cells. Results: Glioblastoma U87 cells with FHL2 or MGMT knockdown were successfully constructed. Compared with the shN group, the proliferation ability in cells of shFHL2-1# or shFHL2-4# group was significantly reduced while the apoptosis rate was significantly elevated (all P<0.01), and the expression of MGMT were significantly reduced (all P<0.01). After TMZ treatment, the expression levels of FHL2 and MGMT in the shN group were significantly increased (both P<0.05), while the proliferation and apoptosis of the cells were not significantly changed (all P>0.05) compared with the corresponding DMSO treatment group. The expression levels of FHL2 and MGMT in the cells of shFHL2-1# and shFHL2-4# groups did not change significantly (all P>0.05), but the cell proliferation capacity was significantly reduced, and the apoptosis level was significantly increased (all P<0.01). Knockdown of MGMT slowed down the proliferation of U87 cells in shN group (P<0.01), while the proliferation capacity of cells of siMGMT-1# and siMGMT-4# groups was further reduced after TMZ treatment (all P<0.01). Conclusion: Interfering with FHL2 expression weakened the proliferation ability of U87 cells and increased the apoptosis rate, and downregulated the expression of MGMT, suggesting that FHL2 may regulate the resistance of U87 cells to TMZ by affecting the expression of MGMT.
Objective: To investigate the effect of interfering the expression of four and a half LIM-only protein 2 (FHL2) on the expression of O6-methylguanine DNA methyltransferase (MGMT) and temozolomide (TMZ) resistance of glioblastoma U87 cells.Methods: Lentiviruses carrying different sequences of FHL2 interference sequences (shFHL2-1#, shFHL2-4#) and negative control (shN) were infected into U87 cells, namely shFHL2-1# group, shFHL2-4# group, and shN group, respectively. siMGMT-1#, siMGMT-4#,and siN were transfected into U87 cells by siRNA transfection technology, namely siMGMT-1# group, siMGMT-4# group, and siN group, respectively. The FHL2 or MGMT knockdown efficiency was verified by qPCR and WB. The above groups of cells were treated with TMZ (the DMSO treatment group was used as the control), and then the proliferation of cells with FHL2 or MGMT knockdown before and after TMZ treatment was detected by CCK-8 method and cell clone formation assay, the apoptosis of cells in FHL2 knockdown group before and after TMZ treatment was detected by flow cytometry. WB method and immunofluorescence method was used to detect the effect of FHL2 knockdown on the expression of MGMT in U87 cells. WB method was used to detect the effect of TMZ treatment on the expression levels of FHL2 and MGMT in each group of cells. Results: Glioblastoma U87 cells with FHL2 or MGMT knockdown were successfully constructed. Compared with the shN group, the proliferation ability in cells of shFHL2-1# or shFHL2-4# group was significantly reduced while the apoptosis rate was significantly elevated (all P<0.01), and the expression of MGMT were significantly reduced (all P<0.01). After TMZ treatment, the expression levels of FHL2 and MGMT in the shN group were significantly increased (both P<0.05), while the proliferation and apoptosis of the cells were not significantly changed (all P>0.05) compared with the corresponding DMSO treatment group. The expression levels of FHL2 and MGMT in the cells of shFHL2-1# and shFHL2-4# groups did not change significantly (all P>0.05), but the cell proliferation capacity was significantly reduced, and the apoptosis level was significantly increased (all P<0.01). Knockdown of MGMT slowed down the proliferation of U87 cells in shN group (P<0.01), while the proliferation capacity of cells of siMGMT-1# and siMGMT-4# groups was further reduced after TMZ treatment (all P<0.01). Conclusion: Interfering with FHL2 expression weakened the proliferation ability of U87 cells and increased the apoptosis rate, and downregulated the expression of MGMT, suggesting that FHL2 may regulate the resistance of U87 cells to TMZ by affecting the expression of MGMT.
4 Establishment and observation of a mouse model of IL-12-CAR-T cell-induced cytokine release syndrome
LI Chencheng
,
LIU Xixi
,
CHEN Biqing
,
TIAN Fang
,
ZHANG Weiguang
,
YANG Jing
,
REN Jiangtao
,
XING Yun
,
ZHU Xuejun
2023, 30(1):28-34.
DOI: 10.3872/j.issn.1007-385X.2023.01.004
Abstract:
Objective：To discuss the method of establishing a cytokine release syndrome (CRS) model by constructing murineoriented chimeric antigen receptor-modified T (CAR-T) cells expressing IL-12 and infusing them back into mice via the tail vein.Methods: CAR molecules targeting murine-derived CD19 were constructed, in which the retroviral vectors were packaged, and then the constructed molecules were used to infect mouse T cells to prepare mCD19-CAR-T and mCD19/IL-12-CAR-T cells. The anti-tumor activity of mCD19/IL-12-CAR-T cells was measured by constructing pancreatic cancer Panc02-CD19 cell transplanted tumor model in mice, and the levels of IL-12 and IFN-γ secreted by two CAR-T cells were detected by ELISA; CRS model was constructed by infusing mCD19/IL-12-CAR-T cells back into the tail vein of the mice. The levels of IL-6, MCP-1, IL-1, IL-10, TNF- α, IFN- γ, and other cytokines in the serum of mice were detected by flow cytometry, and the histopathological changes of liver, spleen, lung, and kidney of the mice were observed by H-E staining. Results: After culture expansion, mCD19/IL-12-CAR-T cells could effectively secrete IL-12,and the CAR positive rate reached (56.9±5.4)%; the modified T cells could efficiently secrete IFN-γ no matter co-cultured with nontargeted Panc02 cells or targeted Panc02-CD19 cells. A mouse pancreatic cancer Panc02-CD19 cell transplanted tumor model was successfully constructed, and the tail vein infusion of 1×106 mCD19/IL-12-CAR-T cells significantly inhibited the growth of the transplanted tumor, but failed to induce severe CRS; after the infusion of 2×106 mCD19/IL-12-CAR-T cells, a series of typical CRS manifestations such as reduced body mass, elevated serum inflammatory factor levels, tissue damage and even death were observed in the mice. Conclusion: The IL-12-CAR-T cell-induced CRS model in mice was successfully constructed, and it is stable and reproducible with wide application prospects.
Objective：To discuss the method of establishing a cytokine release syndrome (CRS) model by constructing murineoriented chimeric antigen receptor-modified T (CAR-T) cells expressing IL-12 and infusing them back into mice via the tail vein.Methods: CAR molecules targeting murine-derived CD19 were constructed, in which the retroviral vectors were packaged, and then the constructed molecules were used to infect mouse T cells to prepare mCD19-CAR-T and mCD19/IL-12-CAR-T cells. The anti-tumor activity of mCD19/IL-12-CAR-T cells was measured by constructing pancreatic cancer Panc02-CD19 cell transplanted tumor model in mice, and the levels of IL-12 and IFN-γ secreted by two CAR-T cells were detected by ELISA; CRS model was constructed by infusing mCD19/IL-12-CAR-T cells back into the tail vein of the mice. The levels of IL-6, MCP-1, IL-1, IL-10, TNF- α, IFN- γ, and other cytokines in the serum of mice were detected by flow cytometry, and the histopathological changes of liver, spleen, lung, and kidney of the mice were observed by H-E staining. Results: After culture expansion, mCD19/IL-12-CAR-T cells could effectively secrete IL-12,and the CAR positive rate reached (56.9±5.4)%; the modified T cells could efficiently secrete IFN-γ no matter co-cultured with nontargeted Panc02 cells or targeted Panc02-CD19 cells. A mouse pancreatic cancer Panc02-CD19 cell transplanted tumor model was successfully constructed, and the tail vein infusion of 1×106 mCD19/IL-12-CAR-T cells significantly inhibited the growth of the transplanted tumor, but failed to induce severe CRS; after the infusion of 2×106 mCD19/IL-12-CAR-T cells, a series of typical CRS manifestations such as reduced body mass, elevated serum inflammatory factor levels, tissue damage and even death were observed in the mice. Conclusion: The IL-12-CAR-T cell-induced CRS model in mice was successfully constructed, and it is stable and reproducible with wide application prospects.
2023, 30(1):35-41.
DOI: 10.3872/j.issn.1007-385X.2023.01.005
Abstract:
Objective: To investigate the role of NOD-like receptor protein 3 (NLRP3) inflammatory vesicle activation in the progression of endometriosis (EMT) to endometriosis-associated ovarian cancer (EAOC) and the mechanism. Methods: EOAC tissues (n=15), EMT tissues (n=15), and normal endometrium tissues (CON, n=15) resected from patients during April 2018 and June 2019, as well as the clinical data of patients, were collected from the Shanghai Changning Maternity and Infant Health Hospital. Expression of NLRP3, BRCA1/BRCA2 containing complex subunit 3 (BRCC3), caspase-1 and IL-1β in the tissues of each group was detected by immunohistochemistry and WB methods. BRCC3 overexpression plasmids and si-BRCC3 plasmids were constructed and transfected into EMT CRL-7566 cells. The expression level of BRCC3 protein in the transfected cells was detected by WB method. The changes in cell proliferation, apoptosis, migration and invasion of transfected cells were detected by MTT method, flow cytometry and Transwell test, respectively. The BRCC3-overexpressing cells were further interfered with NLRP3. The expression levels of BRCC3 and NLRP3 proteins after the interference were detected by WB method, and the changes in cell proliferation, apoptosis, migration and invasion after interference were also detected. Results: The expression levels of NLRP3, caspase-1, IL-1β and BRCC3 in EAOC and EMT tissues were higher than those in CON group (all P<0.01), and there was a positive correlation between the expression of NLRP3 and BRCC3 in EAOC tissues (r=0.65, P<0.01). Overexpression of BRCC3 significantly promoted cell proliferation, migration and invasion and inhibited cell apoptosis in CRL-7566 cells (all P<0.01); While knockdown of BRCC3 had the opposite effects (all P<0.01). Over-expression of BRCC3 increased the expression level of NLRP3 (P<0.01), while interference with BRCC3 inhibited the expression of NLRP3 (P<0.01). Interference with NLRP3 partially attenuated the inhibition on cell apoptosis (P<0.01) and promotion on cell migration (P<0.05) and invasion (P<0.01) brought by BRCC3 overexpression. Conclusion: Both NLRP3 and BRCC3 are highly expressed in EAOC and EMT tissues. Over-expression of BRCC3 can promote the proliferation, migration and invasion but inhibit apoptosis of CRL-7566 cells. BRCC3/NLRP3 is a potential predictivemarker and treatment target for the transformation of EMT to EAOC.
Objective: To investigate the role of NOD-like receptor protein 3 (NLRP3) inflammatory vesicle activation in the progression of endometriosis (EMT) to endometriosis-associated ovarian cancer (EAOC) and the mechanism. Methods: EOAC tissues (n=15), EMT tissues (n=15), and normal endometrium tissues (CON, n=15) resected from patients during April 2018 and June 2019, as well as the clinical data of patients, were collected from the Shanghai Changning Maternity and Infant Health Hospital. Expression of NLRP3, BRCA1/BRCA2 containing complex subunit 3 (BRCC3), caspase-1 and IL-1β in the tissues of each group was detected by immunohistochemistry and WB methods. BRCC3 overexpression plasmids and si-BRCC3 plasmids were constructed and transfected into EMT CRL-7566 cells. The expression level of BRCC3 protein in the transfected cells was detected by WB method. The changes in cell proliferation, apoptosis, migration and invasion of transfected cells were detected by MTT method, flow cytometry and Transwell test, respectively. The BRCC3-overexpressing cells were further interfered with NLRP3. The expression levels of BRCC3 and NLRP3 proteins after the interference were detected by WB method, and the changes in cell proliferation, apoptosis, migration and invasion after interference were also detected. Results: The expression levels of NLRP3, caspase-1, IL-1β and BRCC3 in EAOC and EMT tissues were higher than those in CON group (all P<0.01), and there was a positive correlation between the expression of NLRP3 and BRCC3 in EAOC tissues (r=0.65, P<0.01). Overexpression of BRCC3 significantly promoted cell proliferation, migration and invasion and inhibited cell apoptosis in CRL-7566 cells (all P<0.01); While knockdown of BRCC3 had the opposite effects (all P<0.01). Over-expression of BRCC3 increased the expression level of NLRP3 (P<0.01), while interference with BRCC3 inhibited the expression of NLRP3 (P<0.01). Interference with NLRP3 partially attenuated the inhibition on cell apoptosis (P<0.01) and promotion on cell migration (P<0.05) and invasion (P<0.01) brought by BRCC3 overexpression. Conclusion: Both NLRP3 and BRCC3 are highly expressed in EAOC and EMT tissues. Over-expression of BRCC3 can promote the proliferation, migration and invasion but inhibit apoptosis of CRL-7566 cells. BRCC3/NLRP3 is a potential predictivemarker and treatment target for the transformation of EMT to EAOC.
2023, 30(1):42-49.
DOI: 10.3872/j.issn.1007-385X.2023.01.006
Abstract:
Objective: To investigate the expression of tumor necrosis factor receptor associated protein 1 (TRAP1) in colon cancer tissues and its relationship with clinicopathological features and patient prognosis, as well as the related molecular mechanisms.Methods: The expression of TRAP1 in colon cancer and its relationship with clinicopathological features and patient prognosis were comprehensively analyzed by TCGA and GEO databases. In addition, 10 pairs of colon cancer tissues and corresponding paracancerous tissues surgically resected at the First Hospital of Shanxi Medical University between October 2020 and March 2021 were selected, and the expression of TRAP1 in colon cancer tissues of Chinese was detected by IHC staining for validation. Kaplan-Meier survival analysis was performed by running R package (survivor and survminer); The signal peptide and membrane piercing domain of TRAP1 protein were analyzed by online software, and GO analysis and KEGG analysis were carried out by gene enrichment analysis software.Colon cancer SW480 and SW620 cells were cultured and transfected with si-NC or si-TRAP1, and divided into blank control group,si-NC group and si-TRAP1 group. The TRAP1 expression in colon cancer cells of each group after transfection was detected by qPCR,and the cell cycle and apoptosis of the transfected cells were detected by FCM technique. Results: TRAP1 was highly expressed in colon cancer tissues compared with paracancerous tissues (P<0.01). The expression level of TRAP1 was correlated with lymph node etastasis (P<0.05), and the 5-year overall survival (OS) rate of colon cancer patients with high TRAP1 expression was lower than those with low TRAP1 expression (P<0.05). TRAP1 protein is a cytoplasmic protein, and functional enrichment results showed that TRAP1 and its related molecules are associated with signaling pathways such as cell cycle and ribosome biogenesis (all P<0.01). GSEA enrichment results showed that the levels of colon cancer metabolic reprogramming gene cluster and mitochondrial protein input gene cluster were elevated in the high TRAP1 expression group (all P<0.01). Knockdown of TRAP1 resulted in cell cycle arrest in G1 phase with significantly elevated level of apoptosis of colon cancer cells (all P<0.01). Conclusions: TRAP1 is highly expressed in colon cancer tissues and correlated with lymph node metastasis and dismal OS rate in patients. Knockdown of TRAP1 can block cell cycle and promote apoptosis in colon cancer cells.
Objective: To investigate the expression of tumor necrosis factor receptor associated protein 1 (TRAP1) in colon cancer tissues and its relationship with clinicopathological features and patient prognosis, as well as the related molecular mechanisms.Methods: The expression of TRAP1 in colon cancer and its relationship with clinicopathological features and patient prognosis were comprehensively analyzed by TCGA and GEO databases. In addition, 10 pairs of colon cancer tissues and corresponding paracancerous tissues surgically resected at the First Hospital of Shanxi Medical University between October 2020 and March 2021 were selected, and the expression of TRAP1 in colon cancer tissues of Chinese was detected by IHC staining for validation. Kaplan-Meier survival analysis was performed by running R package (survivor and survminer); The signal peptide and membrane piercing domain of TRAP1 protein were analyzed by online software, and GO analysis and KEGG analysis were carried out by gene enrichment analysis software.Colon cancer SW480 and SW620 cells were cultured and transfected with si-NC or si-TRAP1, and divided into blank control group,si-NC group and si-TRAP1 group. The TRAP1 expression in colon cancer cells of each group after transfection was detected by qPCR,and the cell cycle and apoptosis of the transfected cells were detected by FCM technique. Results: TRAP1 was highly expressed in colon cancer tissues compared with paracancerous tissues (P<0.01). The expression level of TRAP1 was correlated with lymph node etastasis (P<0.05), and the 5-year overall survival (OS) rate of colon cancer patients with high TRAP1 expression was lower than those with low TRAP1 expression (P<0.05). TRAP1 protein is a cytoplasmic protein, and functional enrichment results showed that TRAP1 and its related molecules are associated with signaling pathways such as cell cycle and ribosome biogenesis (all P<0.01). GSEA enrichment results showed that the levels of colon cancer metabolic reprogramming gene cluster and mitochondrial protein input gene cluster were elevated in the high TRAP1 expression group (all P<0.01). Knockdown of TRAP1 resulted in cell cycle arrest in G1 phase with significantly elevated level of apoptosis of colon cancer cells (all P<0.01). Conclusions: TRAP1 is highly expressed in colon cancer tissues and correlated with lymph node metastasis and dismal OS rate in patients. Knockdown of TRAP1 can block cell cycle and promote apoptosis in colon cancer cells.
2023, 30(1):50-54.
DOI: 10.3872/j.issn.1007-385X.2023.01.007
Abstract:
Objective: To explore the impact of liver metastasis on immunotherapy efficacy in patients with advanced gastric cancer.Methods: From February 2019 to January 2022, clinical data of patients with advanced gastric cancer who received immunotherapy in the Cancer Center of Changzhou No.2 People's Hospital affiliated to Nanjing Medical University were collected for this retrospective analysis. The baseline characteristics were compared by Chi-square test or Fisher exact probability method. Chi-square test and KaplanMeier survival analysis were used to compare the therapeutic efficacy and survival time between gastric cancer patients with and without liver metastasis. Results: A total of 48 patients with advanced gastric cancer were included in the analysis, and the patients were divided into a liver metastasis cohort (n=20) and a non-liver metastasis cohort (n=28). The physical condition of patients with liver metastasis was worse than those without liver metastasis. The objective response rates (ORR) in metastasis cohort and non-metastasis cohort were 15.0% and 35.7% (P>0.05), respectively; and the disease control rates (DCR) in these two cohorts were 65.0% and 82.1% (P>0.05), respectively. The median progression-free survival (PFS) was 5.0 and 11.2 months in the two groups (HR=0.40, P<0.05), and the median overall survival (OS) was 12.0 and 19.0 months (P>0.05), respectively. Conclusion: The efficacy of immunotherapy in gastric cancer patients with liver metastasis is worse than that in patients without liver metastasis.
Objective: To explore the impact of liver metastasis on immunotherapy efficacy in patients with advanced gastric cancer.Methods: From February 2019 to January 2022, clinical data of patients with advanced gastric cancer who received immunotherapy in the Cancer Center of Changzhou No.2 People's Hospital affiliated to Nanjing Medical University were collected for this retrospective analysis. The baseline characteristics were compared by Chi-square test or Fisher exact probability method. Chi-square test and KaplanMeier survival analysis were used to compare the therapeutic efficacy and survival time between gastric cancer patients with and without liver metastasis. Results: A total of 48 patients with advanced gastric cancer were included in the analysis, and the patients were divided into a liver metastasis cohort (n=20) and a non-liver metastasis cohort (n=28). The physical condition of patients with liver metastasis was worse than those without liver metastasis. The objective response rates (ORR) in metastasis cohort and non-metastasis cohort were 15.0% and 35.7% (P>0.05), respectively; and the disease control rates (DCR) in these two cohorts were 65.0% and 82.1% (P>0.05), respectively. The median progression-free survival (PFS) was 5.0 and 11.2 months in the two groups (HR=0.40, P<0.05), and the median overall survival (OS) was 12.0 and 19.0 months (P>0.05), respectively. Conclusion: The efficacy of immunotherapy in gastric cancer patients with liver metastasis is worse than that in patients without liver metastasis.
2023, 30(1):55-61.
DOI: 10.3872/j.issn.1007-385X.2023.01.008
Abstract:
Objective: To evaluate the association between the expression of NF-kB inhibitor alpha (NFKBIA) gene and the prognosis and immune infiltration of the tumor microenvironment in patients with skin cutaneous melanoma (SKCM). Methods: GEPIA2 database was used to analyze the differential expression of NFKBIA in SKCM tissues and normal skin tissues. GEPIA2 and Ualcan databases were utilized to analyze the association between NFKBIA expression and SKCM prognosis. TIMER and TISIDB were used to investigate the correlation between NFKBIA and tumor-infiltrating lymphocytes (TIL) and immune regulator genes in SKCM. The association between NFKBIA and subsets of SKCM cells as well as their functional states were analyzed at single-cell level in TISCH and Cancer SEA databases. The paraffin embedded tissues from 14 SKCM patients preserved in Jingmen No.2 People′s Hospital were obtained for this study, and immunohistochemical staining was used to detect the NFKBIA protein expression in SKCM tissues and para-cancerous tissues. Results: NFKBIA was lowly expressed in SKCM tissues, and SKCM patients with low NFKBIA expression had a poor prognosis (P<0.05). NFKBIA expression level was positively correlated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells (all P<0.01). What's more, the expression of NFKBIA was positively correlated with TIL abundance and immunoregulatory genes (all P<0.01). NFKBIA was expressed in SKCM immune cells and positively correlated with cell differentiation and inflammation in tumor microenvironment (R=0.28, 0.23, all P<0.05). Immunohistochemical staining results demonstrated that the protein expression of NFKBIA was significantly lower in SKCM tissues than that in para-cancerous tissues (35.71% vs 85.71%, P<0.05). Conclusions: NFKBIA has a low expression in SKCM tissues, and it is correlated with immune infiltration in SKCM, which can be used as a prognostic marker and treatment target for SKCM.
Objective: To evaluate the association between the expression of NF-kB inhibitor alpha (NFKBIA) gene and the prognosis and immune infiltration of the tumor microenvironment in patients with skin cutaneous melanoma (SKCM). Methods: GEPIA2 database was used to analyze the differential expression of NFKBIA in SKCM tissues and normal skin tissues. GEPIA2 and Ualcan databases were utilized to analyze the association between NFKBIA expression and SKCM prognosis. TIMER and TISIDB were used to investigate the correlation between NFKBIA and tumor-infiltrating lymphocytes (TIL) and immune regulator genes in SKCM. The association between NFKBIA and subsets of SKCM cells as well as their functional states were analyzed at single-cell level in TISCH and Cancer SEA databases. The paraffin embedded tissues from 14 SKCM patients preserved in Jingmen No.2 People′s Hospital were obtained for this study, and immunohistochemical staining was used to detect the NFKBIA protein expression in SKCM tissues and para-cancerous tissues. Results: NFKBIA was lowly expressed in SKCM tissues, and SKCM patients with low NFKBIA expression had a poor prognosis (P<0.05). NFKBIA expression level was positively correlated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells (all P<0.01). What's more, the expression of NFKBIA was positively correlated with TIL abundance and immunoregulatory genes (all P<0.01). NFKBIA was expressed in SKCM immune cells and positively correlated with cell differentiation and inflammation in tumor microenvironment (R=0.28, 0.23, all P<0.05). Immunohistochemical staining results demonstrated that the protein expression of NFKBIA was significantly lower in SKCM tissues than that in para-cancerous tissues (35.71% vs 85.71%, P<0.05). Conclusions: NFKBIA has a low expression in SKCM tissues, and it is correlated with immune infiltration in SKCM, which can be used as a prognostic marker and treatment target for SKCM.
2023, 30(1):62-66.
DOI: 10.3872/j.issn.1007-385X.2023.01.009
Abstract:
免疫球蛋白A（IgA）是最常见抗体之一，并在黏膜表面提供第一道免疫保护。IgA+ B细胞是IgA 产生的主要来源细胞。近年来的研究表明，IgA 在肿瘤发生发展中呈现双向作用，在不同的肿瘤类型及免疫微环境中发挥不同的作用，尤其是IgA+ B细胞和IgA 的促肿瘤和免疫抑制作用成为目前关注的热点及研究的难点。肿瘤微环境（TME）中IgA+ B细胞可通过分泌免疫抑制因子，如IL-10、TGF-β、PD-L1、FASL、IL-35 和Tim1发挥免疫抑制作用。免疫抑制性IgA 在多种肿瘤组织中高表达，并与恶性肿瘤预后差密切相关。本文总结了IgA+ B细胞和IgA 的免疫抑制和促肿瘤作用及其机制，讨论了肿瘤免疫抑制微环境中细胞因子和代谢产物等在调控IgA 类转换重组（CSR）中所起的作用，以及IgA 免疫抑制作用的临床意义，为肿瘤免疫治疗提供新的思路和治疗策略.
免疫球蛋白A（IgA）是最常见抗体之一，并在黏膜表面提供第一道免疫保护。IgA+ B细胞是IgA 产生的主要来源细胞。近年来的研究表明，IgA 在肿瘤发生发展中呈现双向作用，在不同的肿瘤类型及免疫微环境中发挥不同的作用，尤其是IgA+ B细胞和IgA 的促肿瘤和免疫抑制作用成为目前关注的热点及研究的难点。肿瘤微环境（TME）中IgA+ B细胞可通过分泌免疫抑制因子，如IL-10、TGF-β、PD-L1、FASL、IL-35 和Tim1发挥免疫抑制作用。免疫抑制性IgA 在多种肿瘤组织中高表达，并与恶性肿瘤预后差密切相关。本文总结了IgA+ B细胞和IgA 的免疫抑制和促肿瘤作用及其机制，讨论了肿瘤免疫抑制微环境中细胞因子和代谢产物等在调控IgA 类转换重组（CSR）中所起的作用，以及IgA 免疫抑制作用的临床意义，为肿瘤免疫治疗提供新的思路和治疗策略.
2023, 30(1):67-74.
DOI: 10.3872/j.issn.1007-385X.2023.01.010
Abstract:
细菌用于肿瘤治疗虽然是一个传统的研究领域，但在合成生物学理论与技术日趋完善的背景下，以细菌为载体设计新的抗肿瘤靶向与免疫治疗模式，已经形成一个独特的研究方向。特定细菌可以克服物理障碍特异性地靶向和积聚于肿瘤组织中，并可根据临床需要将外源基因导入细菌，实现基因修饰以产生活性蛋白或因子在肿瘤组织中发挥靶向和抗肿瘤免疫效应，从而提高肿瘤治疗的有效性和安全性。同时，细菌疗法不仅可以作为肿瘤治疗的单一疗法，也可与化疗、放疗和免疫治疗联合使用以获得更好的临床疗效。但是，由于肿瘤微环境的多变性与复杂性，需要进一步充分了解相关细菌和肿瘤微环境的免疫特征，进行有针对性的研究，开发出基于细菌的抗肿瘤免疫精准治疗策略，使细菌疗法在临床肿瘤治疗中得到更广泛的应用。
细菌用于肿瘤治疗虽然是一个传统的研究领域，但在合成生物学理论与技术日趋完善的背景下，以细菌为载体设计新的抗肿瘤靶向与免疫治疗模式，已经形成一个独特的研究方向。特定细菌可以克服物理障碍特异性地靶向和积聚于肿瘤组织中，并可根据临床需要将外源基因导入细菌，实现基因修饰以产生活性蛋白或因子在肿瘤组织中发挥靶向和抗肿瘤免疫效应，从而提高肿瘤治疗的有效性和安全性。同时，细菌疗法不仅可以作为肿瘤治疗的单一疗法，也可与化疗、放疗和免疫治疗联合使用以获得更好的临床疗效。但是，由于肿瘤微环境的多变性与复杂性，需要进一步充分了解相关细菌和肿瘤微环境的免疫特征，进行有针对性的研究，开发出基于细菌的抗肿瘤免疫精准治疗策略，使细菌疗法在临床肿瘤治疗中得到更广泛的应用。
11 Research progress on the role of diphtheria toxin and its derivatives in targeted therapy of glioma
2023, 30(1):75-80.
DOI: 10.3872/j.issn.1007-385X.2023.01.011
Abstract:
白喉毒素（DT）及其衍生物可通过受体介导的胞吞转运作用穿越血脑屏障（BBB），并将毒素或药物靶向递送至肿瘤细胞，是有前景的靶向治疗脑胶质瘤的策略之一。目前，用于靶向治疗脑胶质瘤研究的DT衍生物主要有CRM107、DT389-EGF、CRM197、DTAT/DTAT13/DTATEGF和DTEGF13。其中，CRM107 和DT389-EGF已经进入临床Ⅱ期试验，其余衍生物尚处于临床前研究阶段。根据现有研究进展，CRM107 和CRM197 是最有希望在脑胶质瘤治疗中取得突破的两种衍生物，但关键在于降低其毒副作用和提高靶向性。因此，明晰DT及其衍生物在靶向治疗脑胶质瘤的关键作用机制及应用现状，可为促进开发高效低毒的脑胶质瘤治疗药物提供新的思路。
白喉毒素（DT）及其衍生物可通过受体介导的胞吞转运作用穿越血脑屏障（BBB），并将毒素或药物靶向递送至肿瘤细胞，是有前景的靶向治疗脑胶质瘤的策略之一。目前，用于靶向治疗脑胶质瘤研究的DT衍生物主要有CRM107、DT389-EGF、CRM197、DTAT/DTAT13/DTATEGF和DTEGF13。其中，CRM107 和DT389-EGF已经进入临床Ⅱ期试验，其余衍生物尚处于临床前研究阶段。根据现有研究进展，CRM107 和CRM197 是最有希望在脑胶质瘤治疗中取得突破的两种衍生物，但关键在于降低其毒副作用和提高靶向性。因此，明晰DT及其衍生物在靶向治疗脑胶质瘤的关键作用机制及应用现状，可为促进开发高效低毒的脑胶质瘤治疗药物提供新的思路。
2023, 30(1):81-86.
DOI: 10.3872/j.issn.1007-385X.2023.01.012
Abstract:
恶性黑色素瘤（MM）是一种高侵袭性、高致死率的恶性肿瘤。液体活检由于具有样本易获得和创伤性低等优势，在恶性肿瘤诊断和监测中的重要性日益凸显，循环肿瘤DNA（ctDNA）检测正是其中一项新兴起的检测手段。ctDNA在MM诊断和治疗中的临床应用范围十分广泛，包括早期筛查MM人群、帮助检测MM的可驱动基因、监测和评判肿瘤的复发与转移、预测患者对靶向和免疫治疗的反应等。多项研究表明，无论是肿瘤术后辅助治疗还是晚期治疗的肿瘤患者，ctDNA 能更好地反映肿瘤的异质性，提供预后相关信息，更早判断疾病的复发与转移，能准确评估对治疗的反应并确定耐药机制等。虽然目前尚未出现基于ctDNA 的MM诊治共识，相关研究结论仍需要在前瞻性临床试验中继续验证，但是ctDNA 检测为MM患者的临床管理提供了新的选择，不久或将用于进一步完善MM的诊断和治疗。
恶性黑色素瘤（MM）是一种高侵袭性、高致死率的恶性肿瘤。液体活检由于具有样本易获得和创伤性低等优势，在恶性肿瘤诊断和监测中的重要性日益凸显，循环肿瘤DNA（ctDNA）检测正是其中一项新兴起的检测手段。ctDNA在MM诊断和治疗中的临床应用范围十分广泛，包括早期筛查MM人群、帮助检测MM的可驱动基因、监测和评判肿瘤的复发与转移、预测患者对靶向和免疫治疗的反应等。多项研究表明，无论是肿瘤术后辅助治疗还是晚期治疗的肿瘤患者，ctDNA 能更好地反映肿瘤的异质性，提供预后相关信息，更早判断疾病的复发与转移，能准确评估对治疗的反应并确定耐药机制等。虽然目前尚未出现基于ctDNA 的MM诊治共识，相关研究结论仍需要在前瞻性临床试验中继续验证，但是ctDNA 检测为MM患者的临床管理提供了新的选择，不久或将用于进一步完善MM的诊断和治疗。
2023, 30(1):87-90.
DOI: 10.3872/j.issn.1007-385X.2023.01.013
Abstract:
弥漫硬化型甲状腺乳头状癌（DSV-PTC）是甲状腺乳头状癌的少见病例亚型，其特征为双侧甲状腺弥漫增大，目前术前检测技术尚不足以精准诊断出其较强的恶性程度及风险分层。作为液体活检的代表性技术之一的循环肿瘤细胞（CTCs）检测，可作为DSV-PTC 的非侵入性肿瘤检测手段，实现高危型甲状腺乳头状癌的术前精准诊断。本研究通过术前采集1例DSV-PTC患者外周血，以TumorFisher 技术检测CTCs，结果检到30 个CTCs，提示其恶性程度较高和转移风险较大；术后病理诊断为DSV-PTC且ATA分层为高风险，与术前CTCs 检测结果一致。由此可见，CTCs 检测可在术前精准预测该患者有较高风险及较强的恶性程度，进而辅助临床医生实现正确诊断和精准治疗方案的制定。
弥漫硬化型甲状腺乳头状癌（DSV-PTC）是甲状腺乳头状癌的少见病例亚型，其特征为双侧甲状腺弥漫增大，目前术前检测技术尚不足以精准诊断出其较强的恶性程度及风险分层。作为液体活检的代表性技术之一的循环肿瘤细胞（CTCs）检测，可作为DSV-PTC 的非侵入性肿瘤检测手段，实现高危型甲状腺乳头状癌的术前精准诊断。本研究通过术前采集1例DSV-PTC患者外周血，以TumorFisher 技术检测CTCs，结果检到30 个CTCs，提示其恶性程度较高和转移风险较大；术后病理诊断为DSV-PTC且ATA分层为高风险，与术前CTCs 检测结果一致。由此可见，CTCs 检测可在术前精准预测该患者有较高风险及较强的恶性程度，进而辅助临床医生实现正确诊断和精准治疗方案的制定。
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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
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- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.