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Volume 32,Issue 1,2025 Table of Contents
2025, 32(1):1-8.
DOI: 10.3872/j.issn.1007-385X.2025.01.001
Abstract:
[Abstract] Chimeric antigen receptor natural killer (CAR-NK) cell therapy, as an emerging cellular immunotherapy strategy, has demonstrated a broader clinical application potential compared to CAR-T cell therapy due to its high safety profile and the unique advantages of 'off-the-shelf ' preparation. This article thoroughly discusses the antitumor mechanisms of CAR-NK cells, elucidating their targeted recognition mechanism, inherent cytotoxic activity, and the latest advancements in optimizing specific receptors to enhance their adaptability within the tumor microenvironment. Additionally, it provides an in-depth analysis of the advantages and challenges of various sources for CAR-NK cells, including peripheral blood, umbilical cord blood, induced pluripotent stem cells (iPSCs), and NK-92 cells, while summarizing their major challenges in the tumor immune microenvironment, such as insufficient persistence, immune suppression, and antigen heterogeneity. Finally, this article presents the therapeutic potential, limitations, and future perspectives of CAR-NK therapy in treating solid tumors, with a focus on its ongoing development and clinical translation.
[Abstract] Chimeric antigen receptor natural killer (CAR-NK) cell therapy, as an emerging cellular immunotherapy strategy, has demonstrated a broader clinical application potential compared to CAR-T cell therapy due to its high safety profile and the unique advantages of 'off-the-shelf ' preparation. This article thoroughly discusses the antitumor mechanisms of CAR-NK cells, elucidating their targeted recognition mechanism, inherent cytotoxic activity, and the latest advancements in optimizing specific receptors to enhance their adaptability within the tumor microenvironment. Additionally, it provides an in-depth analysis of the advantages and challenges of various sources for CAR-NK cells, including peripheral blood, umbilical cord blood, induced pluripotent stem cells (iPSCs), and NK-92 cells, while summarizing their major challenges in the tumor immune microenvironment, such as insufficient persistence, immune suppression, and antigen heterogeneity. Finally, this article presents the therapeutic potential, limitations, and future perspectives of CAR-NK therapy in treating solid tumors, with a focus on its ongoing development and clinical translation.
2025, 32(1):9-13.
DOI: 10.3872/j.issn.1007-385X.2025.01.002
Abstract:
[Abstract] Since 2017, twelve chimeric antigen receptor gene-modified T lymphocyte (CAR-T cell) products have been approved for the treatment of hematological malignancies, including relapsed/refractory acute B lymphoblastic leukemia (B-ALL), specific subtypes of B cell lymphoma, and multiple myeloma. However, CAR-T cell therapy faces numerous challenges in its clinical application, such as resistance, lengthy production cycles, high individuation and costs in hematological tumors, and tumor heterogeneity/antigen escape, insufficient infiltration capability, immunosuppressive microenvironments, and poor therapeutic response in solid tumors. With the in-depth exploration of tumor immunology and the development of genetic engineering technology, various new strategies have been attempted to enhance the efficacy and generalizability of CAR-T cell therapy. This paper presents a commentary on CAR-T cell therapy, with a focus on key clinical issues and corresponding countermeasures, providing valuable insights for future basic research and clinical transformation of CAR-T cell therapy.
[Abstract] Since 2017, twelve chimeric antigen receptor gene-modified T lymphocyte (CAR-T cell) products have been approved for the treatment of hematological malignancies, including relapsed/refractory acute B lymphoblastic leukemia (B-ALL), specific subtypes of B cell lymphoma, and multiple myeloma. However, CAR-T cell therapy faces numerous challenges in its clinical application, such as resistance, lengthy production cycles, high individuation and costs in hematological tumors, and tumor heterogeneity/antigen escape, insufficient infiltration capability, immunosuppressive microenvironments, and poor therapeutic response in solid tumors. With the in-depth exploration of tumor immunology and the development of genetic engineering technology, various new strategies have been attempted to enhance the efficacy and generalizability of CAR-T cell therapy. This paper presents a commentary on CAR-T cell therapy, with a focus on key clinical issues and corresponding countermeasures, providing valuable insights for future basic research and clinical transformation of CAR-T cell therapy.
2025, 32(1):14-23.
DOI: 10.3872/j.issn.1007-385X.2025.01.003
Abstract:
[Abstract] Small cell lung cancer (SCLC) is the most aggressive type of lung cancer, accounting for approximately 13% to 15% of all lung cancer cases. Although SCLC patients are highly responsive to chemotherapy and radiotherapy at their initial treatment, they are prone to relapse, leading to a low survival rate. Since 2018, with the success of the IMpower133 and CASPIAN trials, SCLC has entered the era of immunotherapy. Chemotherapy combined with immune checkpoint inhibitors (ICIs) has become the standard firstline treatment for extensive-stage SCLC. Meanwhile, immunotherapy has also achieved preliminary success in limited-stage SCLC. Despite some progress in SCLC immunotherapy, the overall survival benefit remains limited. There is a lack of effective predictive biomarkers, and treatment options for relapsed/refractory SCLC are scarce, posing significant challenges to the future of immunotherapy in SCLC. In this article, the latest clinical research on SCLC immunotherapy, both domestically and internationally, is reviewed, different types of immunotherapeutic agents, biomarkers, and novel immunotherapy targets are analyzed, and the combination strategies and future prospects of SCLC immunotherapy are discussed.
[Abstract] Small cell lung cancer (SCLC) is the most aggressive type of lung cancer, accounting for approximately 13% to 15% of all lung cancer cases. Although SCLC patients are highly responsive to chemotherapy and radiotherapy at their initial treatment, they are prone to relapse, leading to a low survival rate. Since 2018, with the success of the IMpower133 and CASPIAN trials, SCLC has entered the era of immunotherapy. Chemotherapy combined with immune checkpoint inhibitors (ICIs) has become the standard firstline treatment for extensive-stage SCLC. Meanwhile, immunotherapy has also achieved preliminary success in limited-stage SCLC. Despite some progress in SCLC immunotherapy, the overall survival benefit remains limited. There is a lack of effective predictive biomarkers, and treatment options for relapsed/refractory SCLC are scarce, posing significant challenges to the future of immunotherapy in SCLC. In this article, the latest clinical research on SCLC immunotherapy, both domestically and internationally, is reviewed, different types of immunotherapeutic agents, biomarkers, and novel immunotherapy targets are analyzed, and the combination strategies and future prospects of SCLC immunotherapy are discussed.
2025, 32(1):24-29.
DOI: 10.3872/j.issn.1007-385X.2025.01.004
Abstract:
[Abstract] Immune cell-mediated delivery system employs immune cells as carriers to deliver therapeutic drugs to specific lesion sites by leveraging the innate chemotaxis of these cells. Due to its excellent biocompatibility, low immunogenicity, tissue-specific homing, and ability to cross biological barriers, this approach has emerged as an important strategy for drug delivery and disease treatment. This article systematically discusses the drug delivery strategies of immune cells, the biological characteristics, advantages, and disadvantages of using monocytes, neutrophils, mesenchymal stem cells, and dendritic cells as carrier cells, as well as the latest research progresses on their application in tumor treatment. This review provides valuable insights for further studies on immune cell-mediated drug delivery systems and their clinical transformation.
[Abstract] Immune cell-mediated delivery system employs immune cells as carriers to deliver therapeutic drugs to specific lesion sites by leveraging the innate chemotaxis of these cells. Due to its excellent biocompatibility, low immunogenicity, tissue-specific homing, and ability to cross biological barriers, this approach has emerged as an important strategy for drug delivery and disease treatment. This article systematically discusses the drug delivery strategies of immune cells, the biological characteristics, advantages, and disadvantages of using monocytes, neutrophils, mesenchymal stem cells, and dendritic cells as carrier cells, as well as the latest research progresses on their application in tumor treatment. This review provides valuable insights for further studies on immune cell-mediated drug delivery systems and their clinical transformation.
2025, 32(1):30-37.
DOI: 10.3872/j.issn.1007-385X.2025.01.005
Abstract:
[Abstract] Thyroid cancer is the most prevalent malignant tumor of the endocrine system, and its incidence has shown a significant upward trend in recent years. Acetylation, an important post-translational protein modification, is involved in regulating gene transcription, cell cycle progression, and invasion ability in various types of thyroid cancers. Additionally, histone deacetylase (HDAC) inhibitors have shown potential in the treatment of thyroid cancer. This article systematically reviews the biological functions and regulatory mechanisms of acetylation in the development and progression of thyroid cancer based on recent literature. Furthermore, it discusses the clinical application prospects of HDAC inhibitors, providing a solid theoretical basis and feasible therapeutic strategies for targeted therapy of thyroid cancer.
[Abstract] Thyroid cancer is the most prevalent malignant tumor of the endocrine system, and its incidence has shown a significant upward trend in recent years. Acetylation, an important post-translational protein modification, is involved in regulating gene transcription, cell cycle progression, and invasion ability in various types of thyroid cancers. Additionally, histone deacetylase (HDAC) inhibitors have shown potential in the treatment of thyroid cancer. This article systematically reviews the biological functions and regulatory mechanisms of acetylation in the development and progression of thyroid cancer based on recent literature. Furthermore, it discusses the clinical application prospects of HDAC inhibitors, providing a solid theoretical basis and feasible therapeutic strategies for targeted therapy of thyroid cancer.
2025, 32(1):38-47.
DOI: 10.3872/j.issn.1007-385X.2025.01.006
Abstract:
[Abstract] Objective: To investigate the effects of KH-type splicing regulatory protein (KHSRP) targeting and regulating JAK1/ STAT3 signaling axis on the proliferation, migration and invasion of the adenocarcinoma of esophagogastric junction (AEG) cells, as well as the growth of transplanted tumors and lung metastasis. Methods: A total of 64 pairs of AEG tissue and adjacent normal tissue samples, along with clinical data from patients diagnosed at Huaihe Hospital from January 2017 to December 2018 were collected. The expression level of KHSRP in AEG tissues and adjacent normal tissues was observed using immunohistochemical staining. The differential expression of KHSRP in AEG cells (OE-19, TE-7, BIC-1, FLO-1, SK-GT-4, BE-3) and normal esophageal epithelial cells (Het-1A) was detected by qPCR. Lentiviral vectors were used to knockdown and overexpress KHSRP in OE-19, TE-7, FLO-1, and SK-GT-4 cells. The experiment was divided into the following groups:sh-NC group, sh-KHSRP group, Vector group, and KHSRP overexpression group (KHSRP group). The knockdown or overexpression efficiency was detected by qPCR, and the effects of KHSRP knockdown or overexpression on AEG cell proliferation, migration and invasion were evaluated using CCK-8 and Transwell assays, respectively. A mouse xenograft and lung metastasis model was established to observe the effects of KHSRP on tumor growth and metastasis in vivo. The targeted regulation of JAK/STAT signaling pathway by KHSRP was verified by Western blotting. A rescue experiment was conducted to verify whether KHSRP promoted malignant progression of AEG cells through the JAK1/STAT3 signaling pathway. Results: Compared with adjacent normal tissues, the expression level of KHSRP in AEG tissues was significantly increased (P < 0.05 or P < 0.01). Cell function experiments showed that KHSRP overexpression significantly promoted AEG cell proliferation, migration, and invasion in vitro (P < 0.05 or P < 0.01). In vivo animal experiments showed that KHSRP promoted AEG cell xenograft tumor growth and lung metastasis in nude mice (P < 0.05 or P < 0.01). After KHSRP knockdown, the phosphorylation levels of JAK1 and STAT3 in the JAK/STAT signaling pathway were significantly reduced, while overexpression of KHSRP led to the opposite results (P < 0.05 or P < 0.01). Rescue experiment showed that KHSRP could reverse the inhibition of cell proliferation, migration, and invasion caused by JAK1/STAT3 knockdown (P < 0.05 or P < 0.01). Conclusion: KHSRP regulates the malignant progression of AEG cells by activating JAK1/STAT3 signaling axis. KHSRP may become a potential target for the clinical treatment of AEG.
[Abstract] Objective: To investigate the effects of KH-type splicing regulatory protein (KHSRP) targeting and regulating JAK1/ STAT3 signaling axis on the proliferation, migration and invasion of the adenocarcinoma of esophagogastric junction (AEG) cells, as well as the growth of transplanted tumors and lung metastasis. Methods: A total of 64 pairs of AEG tissue and adjacent normal tissue samples, along with clinical data from patients diagnosed at Huaihe Hospital from January 2017 to December 2018 were collected. The expression level of KHSRP in AEG tissues and adjacent normal tissues was observed using immunohistochemical staining. The differential expression of KHSRP in AEG cells (OE-19, TE-7, BIC-1, FLO-1, SK-GT-4, BE-3) and normal esophageal epithelial cells (Het-1A) was detected by qPCR. Lentiviral vectors were used to knockdown and overexpress KHSRP in OE-19, TE-7, FLO-1, and SK-GT-4 cells. The experiment was divided into the following groups:sh-NC group, sh-KHSRP group, Vector group, and KHSRP overexpression group (KHSRP group). The knockdown or overexpression efficiency was detected by qPCR, and the effects of KHSRP knockdown or overexpression on AEG cell proliferation, migration and invasion were evaluated using CCK-8 and Transwell assays, respectively. A mouse xenograft and lung metastasis model was established to observe the effects of KHSRP on tumor growth and metastasis in vivo. The targeted regulation of JAK/STAT signaling pathway by KHSRP was verified by Western blotting. A rescue experiment was conducted to verify whether KHSRP promoted malignant progression of AEG cells through the JAK1/STAT3 signaling pathway. Results: Compared with adjacent normal tissues, the expression level of KHSRP in AEG tissues was significantly increased (P < 0.05 or P < 0.01). Cell function experiments showed that KHSRP overexpression significantly promoted AEG cell proliferation, migration, and invasion in vitro (P < 0.05 or P < 0.01). In vivo animal experiments showed that KHSRP promoted AEG cell xenograft tumor growth and lung metastasis in nude mice (P < 0.05 or P < 0.01). After KHSRP knockdown, the phosphorylation levels of JAK1 and STAT3 in the JAK/STAT signaling pathway were significantly reduced, while overexpression of KHSRP led to the opposite results (P < 0.05 or P < 0.01). Rescue experiment showed that KHSRP could reverse the inhibition of cell proliferation, migration, and invasion caused by JAK1/STAT3 knockdown (P < 0.05 or P < 0.01). Conclusion: KHSRP regulates the malignant progression of AEG cells by activating JAK1/STAT3 signaling axis. KHSRP may become a potential target for the clinical treatment of AEG.
2025, 32(1):48-55.
DOI: 10.3872/j.issn.1007-385X.2025.01.007
Abstract:
[Abstract] Objective: To investigate the effect of protein tyrosine phosphatase D (PTPRD) demethylation on the proliferation, migration, and chemoresistance of gastric cancer (GC) cells through the phosphatidyl inositol 3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. Methods: The gastric cancer MKN-74 and MKN-45 cells, as well as human gastric mucosal epithelial GES-1 cells, GES-1 were cultured in vitro and PTPRD expression was detected. MKN-45 cells and their drug-resistant variant MKN-45/ 5-FU cells were routinely cultured and transfected with various vectors: PTPRD empty vector (NC group, NC/5-FU group), PTPRD overexpressing adenovirus (PTPRD group, PTPRD/5-FU group), shRNA empty vector (sh-NC group, sh-NC/5-FU group), shRNA PTPRD lentivirus (sh-PTPRD group, sh-PTPRD/5-FU group), and PTPRD overexpressing adenovirus + 10 μmol/L 740Y-P treatment (PTPRD + 740Y-P group, PTPRD + 740Y-P/5-FU group). MTT assay and wound healing assay were used to assess cell proliferation and migration. Cell autophagy levels were assessed using autophagy assay, and the expression of epithelial-mesenchymal transition (EMT) and PI3K/Akt/mTOR pathway related proteins was detected using western blot (WB). MKN-45 cells were treated with 0, 2.5, 5, 10, 20 and 40 μmol/L 5-aza solutions, and the PTPRD mRNA expression and cell proliferation in MKN-45 cells were detected using qPCR and MTT assays. Results: PTPRD mRNA and protein were significantly downregulated in gastric cancer cells (P < 0.05). Compared with the MKN-45 group, the numbers of autophagosomes and autophagosomes, as well as the protein expression of PTPRD, E-cadherin, and BAX significantly increased in the PTPRD group (all P < 0.05), while cell proliferation, migration rate, and protein expression of p-PI3K, vimentin, p-Akt, and p-mTOR decreased significantly (all P < 0.05); However, in the sh-PTPRD group, cell proliferation activity, migration rate, and protein expression of p-PI3K, vimentin, p-Akt, and p-mTOR increased notably, while the quantity of autophagosomes, autophagosomes, and protein expression of PTPRD, E-cadherin, and BAX decreased (all P < 0.05). Compared with the PTPRD group, the PTPRD + 740Y-P group showed an increase in cell proliferation activity, migration rate, protein expression of p-PI3K, vimentin, p-Akt, and p-mTOR (all P < 0.05), and a decrease in number of autophagosomes, autophagosomes, and protein expression of PTPRD, E-cadherin, and BAX (all P < 0.05). With the increase of 5-aza concentration, the mRNA expression of PTPRD in MKN-45 cells increased (P < 0.05), while the cell proliferation activity decreased (P < 0.05). Compared with the MKN-45/5-FU group, the cell migration rate and proliferation activity decreased in PTPRD/5-FU group, while the sh-PTPRD/5-FU group showed an increase in cell migration rate and proliferation activity (all P < 0.05). Compared with the PTPRD/5-FU group, the PTPRD + 740Y-P/5-FU group showed an increase in cell migration rate and proliferation activity (all P < 0.05). Conclusion: PTPRD is downregulated in GC cells, and its demethylation may inhibit proliferation and migration of GC cells and enhance chemosensitivity by suppressing the PI3K/Akt/mTOR pathway.
[Abstract] Objective: To investigate the effect of protein tyrosine phosphatase D (PTPRD) demethylation on the proliferation, migration, and chemoresistance of gastric cancer (GC) cells through the phosphatidyl inositol 3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. Methods: The gastric cancer MKN-74 and MKN-45 cells, as well as human gastric mucosal epithelial GES-1 cells, GES-1 were cultured in vitro and PTPRD expression was detected. MKN-45 cells and their drug-resistant variant MKN-45/ 5-FU cells were routinely cultured and transfected with various vectors: PTPRD empty vector (NC group, NC/5-FU group), PTPRD overexpressing adenovirus (PTPRD group, PTPRD/5-FU group), shRNA empty vector (sh-NC group, sh-NC/5-FU group), shRNA PTPRD lentivirus (sh-PTPRD group, sh-PTPRD/5-FU group), and PTPRD overexpressing adenovirus + 10 μmol/L 740Y-P treatment (PTPRD + 740Y-P group, PTPRD + 740Y-P/5-FU group). MTT assay and wound healing assay were used to assess cell proliferation and migration. Cell autophagy levels were assessed using autophagy assay, and the expression of epithelial-mesenchymal transition (EMT) and PI3K/Akt/mTOR pathway related proteins was detected using western blot (WB). MKN-45 cells were treated with 0, 2.5, 5, 10, 20 and 40 μmol/L 5-aza solutions, and the PTPRD mRNA expression and cell proliferation in MKN-45 cells were detected using qPCR and MTT assays. Results: PTPRD mRNA and protein were significantly downregulated in gastric cancer cells (P < 0.05). Compared with the MKN-45 group, the numbers of autophagosomes and autophagosomes, as well as the protein expression of PTPRD, E-cadherin, and BAX significantly increased in the PTPRD group (all P < 0.05), while cell proliferation, migration rate, and protein expression of p-PI3K, vimentin, p-Akt, and p-mTOR decreased significantly (all P < 0.05); However, in the sh-PTPRD group, cell proliferation activity, migration rate, and protein expression of p-PI3K, vimentin, p-Akt, and p-mTOR increased notably, while the quantity of autophagosomes, autophagosomes, and protein expression of PTPRD, E-cadherin, and BAX decreased (all P < 0.05). Compared with the PTPRD group, the PTPRD + 740Y-P group showed an increase in cell proliferation activity, migration rate, protein expression of p-PI3K, vimentin, p-Akt, and p-mTOR (all P < 0.05), and a decrease in number of autophagosomes, autophagosomes, and protein expression of PTPRD, E-cadherin, and BAX (all P < 0.05). With the increase of 5-aza concentration, the mRNA expression of PTPRD in MKN-45 cells increased (P < 0.05), while the cell proliferation activity decreased (P < 0.05). Compared with the MKN-45/5-FU group, the cell migration rate and proliferation activity decreased in PTPRD/5-FU group, while the sh-PTPRD/5-FU group showed an increase in cell migration rate and proliferation activity (all P < 0.05). Compared with the PTPRD/5-FU group, the PTPRD + 740Y-P/5-FU group showed an increase in cell migration rate and proliferation activity (all P < 0.05). Conclusion: PTPRD is downregulated in GC cells, and its demethylation may inhibit proliferation and migration of GC cells and enhance chemosensitivity by suppressing the PI3K/Akt/mTOR pathway.
2025, 32(1):56-63.
DOI: 10.3872/j.issn.1007-385X.2025.01.008
Abstract:
[Abstract] Objective: To investigate the role of methionine adenosyltransferase 2 (MAT2A) in esophageal squamous cell carcinoma (ESCC) and evaluate the inhibitory effects of MAT2A inhibitor PF9366 on ESCC cells and its underlying molecular mechanisms. Methods: Human ESCC cell lines (KYSE450, KYSE510, KYSE180, and KYSE410) and normal esophageal epithelial cells (NEECs) were used in this study. S-adenosylmethionine (SAM) production in these cells was verified by ELISA assay. KYSE450 and KYSE510 cells were treated with various concentrations of PF9366 (0, 5, 10, and 25 μmol/L). The inhibitory effects of PF9366 on methionine (MET) activity and proliferation of ESCC cells were assessed using ELISA, MTS assay, and plate cloning formation assay. RNA-seq was performed to observe the effects of PF9366 on downstream oncogenic signaling pathways in KYSE450 cells. KYSE450 and KYSE510 cell xenograft models were constructed in mice to observe the effects of PF9366 on tumor growth in vivo. Results: MET activity in ESCC cells was significantly higher than that in NEECs (P < 0.01). Following PF9366 treatment, SAM activity and cellular proliferation in KYSE450 and KYSE510 cells were significantly inhibited (all P < 0.01), with a clear dose-dependent inhibitory effect (all P < 0.05). RNA-seq analysis revealed that 20 signaling pathways associated with carcinogenesis and progression were downregulated in PF9366-treated ESCC cells. In vivo xenograft experiments demonstrated that PF9366 treatment significantly inhibited the growth of ESCC cell-derived tumors in mice (all P < 0.0001). Conclusion: MAT2A inhibitor PF9366 inhibits SAM production in ESCC cells, suppresses cell proliferation, and activates key downstream oncogenic signaling networks, suggesting that MAT2A, a key enzyme in methionine metabolism, is a potential therapeutic target for ESCC.
[Abstract] Objective: To investigate the role of methionine adenosyltransferase 2 (MAT2A) in esophageal squamous cell carcinoma (ESCC) and evaluate the inhibitory effects of MAT2A inhibitor PF9366 on ESCC cells and its underlying molecular mechanisms. Methods: Human ESCC cell lines (KYSE450, KYSE510, KYSE180, and KYSE410) and normal esophageal epithelial cells (NEECs) were used in this study. S-adenosylmethionine (SAM) production in these cells was verified by ELISA assay. KYSE450 and KYSE510 cells were treated with various concentrations of PF9366 (0, 5, 10, and 25 μmol/L). The inhibitory effects of PF9366 on methionine (MET) activity and proliferation of ESCC cells were assessed using ELISA, MTS assay, and plate cloning formation assay. RNA-seq was performed to observe the effects of PF9366 on downstream oncogenic signaling pathways in KYSE450 cells. KYSE450 and KYSE510 cell xenograft models were constructed in mice to observe the effects of PF9366 on tumor growth in vivo. Results: MET activity in ESCC cells was significantly higher than that in NEECs (P < 0.01). Following PF9366 treatment, SAM activity and cellular proliferation in KYSE450 and KYSE510 cells were significantly inhibited (all P < 0.01), with a clear dose-dependent inhibitory effect (all P < 0.05). RNA-seq analysis revealed that 20 signaling pathways associated with carcinogenesis and progression were downregulated in PF9366-treated ESCC cells. In vivo xenograft experiments demonstrated that PF9366 treatment significantly inhibited the growth of ESCC cell-derived tumors in mice (all P < 0.0001). Conclusion: MAT2A inhibitor PF9366 inhibits SAM production in ESCC cells, suppresses cell proliferation, and activates key downstream oncogenic signaling networks, suggesting that MAT2A, a key enzyme in methionine metabolism, is a potential therapeutic target for ESCC.
2025, 32(1):64-72.
DOI: 10.3872/j.issn.1007-385X.2025.01.009
Abstract:
[Abstract] Objective: To investigate the biological role of miR-1224-5p in the proliferation, migration and apoptosis of prostate cancer cells, as well as its regulatory mechanism of expression. Methods: Human prostate cancer cells (PC3, DU145, LNCaP, 22Rv1) and normal prostate epithelial RWPE-1 cells were selected for this study. The expression of miR-1224-5p in prostate cancer cells was detected by qPCR. miR-1224-5p mimic, inhibitor and corresponding negative control (NC) plasmids were transfected into PC3 and DU145 cells by liposome transfection technology, respectively. The transfection efficiency was verified by qPCR. The effects of miR-1224-5p mimic and inhibitor on cell proliferation, migration and apoptosis were detected by CCK-8 assay, plate clone formation assay, scratch healing assay and flow cytometry. The potential N6 -methyladenosine (m6 A) modification sites in the pri-miR-1224-5p sequence were predicted using SRAMP website, and the prediction results were verified using methylated RNA immunoprecipitation (MeRIP). The expression of methyltransferase 3 (METTL3), a key methyltransferase involved in m6 A modification, in prostate cancer cells was detected by qPCR. CCK-8 assay and Transwell assay were used to detect the effect of METTL3 siRNA transfection on the proliferation and migration of PC3 and DU145 cells. The regulatory effect of METTL3-mediated m6 A modification on the expression of miR-1224-5p was detected by qPCR and MeRIP. Results: miR-1224-5p was upregulated in prostate cancer cells (all P < 0.01). Transfection with miR-1224-5p mimic promoted the proliferation, migration and inhibited the apoptosis of PC3 and DU145 cells (P < 0.05 or P < 0.01). Conversely, miR-1224-5p inhibitor suppressed the proliferation, migration and induced apoptosis of PC3 and DU145 cells (P < 0.05 or P < 0.01). pri-miR-1224-5p contained m6 A modification sites. METTL3 was highly expressed in prostate cancer cells (all P < 0.01). Transfection of METTL3 siRNA inhibited the proliferation and migration of PC3 and DU145 cells (all P < 0.01). METTL3-mediated m6 A modification regulated the expression of miR-1224-5p. Conclusion: miR-1224-5p is upregulated in prostate cancer cells through METTL3-mediated m6 A modification. Down-regulation of miR-1224-5p can inhibit the proliferation, migration and induce apoptosis of prostate cancer cells.
[Abstract] Objective: To investigate the biological role of miR-1224-5p in the proliferation, migration and apoptosis of prostate cancer cells, as well as its regulatory mechanism of expression. Methods: Human prostate cancer cells (PC3, DU145, LNCaP, 22Rv1) and normal prostate epithelial RWPE-1 cells were selected for this study. The expression of miR-1224-5p in prostate cancer cells was detected by qPCR. miR-1224-5p mimic, inhibitor and corresponding negative control (NC) plasmids were transfected into PC3 and DU145 cells by liposome transfection technology, respectively. The transfection efficiency was verified by qPCR. The effects of miR-1224-5p mimic and inhibitor on cell proliferation, migration and apoptosis were detected by CCK-8 assay, plate clone formation assay, scratch healing assay and flow cytometry. The potential N6 -methyladenosine (m6 A) modification sites in the pri-miR-1224-5p sequence were predicted using SRAMP website, and the prediction results were verified using methylated RNA immunoprecipitation (MeRIP). The expression of methyltransferase 3 (METTL3), a key methyltransferase involved in m6 A modification, in prostate cancer cells was detected by qPCR. CCK-8 assay and Transwell assay were used to detect the effect of METTL3 siRNA transfection on the proliferation and migration of PC3 and DU145 cells. The regulatory effect of METTL3-mediated m6 A modification on the expression of miR-1224-5p was detected by qPCR and MeRIP. Results: miR-1224-5p was upregulated in prostate cancer cells (all P < 0.01). Transfection with miR-1224-5p mimic promoted the proliferation, migration and inhibited the apoptosis of PC3 and DU145 cells (P < 0.05 or P < 0.01). Conversely, miR-1224-5p inhibitor suppressed the proliferation, migration and induced apoptosis of PC3 and DU145 cells (P < 0.05 or P < 0.01). pri-miR-1224-5p contained m6 A modification sites. METTL3 was highly expressed in prostate cancer cells (all P < 0.01). Transfection of METTL3 siRNA inhibited the proliferation and migration of PC3 and DU145 cells (all P < 0.01). METTL3-mediated m6 A modification regulated the expression of miR-1224-5p. Conclusion: miR-1224-5p is upregulated in prostate cancer cells through METTL3-mediated m6 A modification. Down-regulation of miR-1224-5p can inhibit the proliferation, migration and induce apoptosis of prostate cancer cells.
2025, 32(1):73-78.
DOI: 10.3872/j.issn.1007-385X.2025.01.010
Abstract:
[Abstract] Objective: To explore the value of lymphocyte subsets in predicting the efficacy and prognosis of non-small cell lung cancer (NSCLC) patients receiving programmed death receptor 1 (PD-1) monoclonal antibody (mAb) combined with chemotherapy. Methods: A retrospective analysis was conducted on the clinical data of 50 NSCLC patients diagnosed and treated with PD-1 mAb combined with chemotherapy at the Second Hospital of Lanzhou University from January 2022 to December 2023. Peripheral blood lymphocyte subsets (including total T cells, CD4+ T cells, CD8+ T cells, NK cells, total B lymphocytes, and CD4+ /CD8+ T cell ratio) were collected before and after two cycles of treatment. After two cycles of treatment, imaging examination was performed to evaluate the therapeutic efficacy, dividing patients into disease control (DC) group and disease progression (PD) group. The relationship between lymphocyte subset levels and the short-term efficacy in NSCLC patients was analyzed using chi-square test, rank sum test, and Logistic regression analysis. The value of lymphocyte subsets in predicting patients’ progression-free survival (PFS) was explored using KaplanMeier method. Results: PD-1 mAb combined with chemotherapy significantly influenced the immune status of NSCLC patients. After treatment, the peripheral blood CD4+ T cells and CD4+ /CD8+ T cell ratio significantly increased (both P < 0.01), while the level of CD8+ T cells decreased. In terms of short-term efficacy, the proportion of CD4+ T cells and the CD4+ /CD8+ T cell ratio in the DC group were significantly higher than those in the PD group (both P < 0.01). Logistic multivariate analysis showed that the CD4+ /CD8+ T cell ratio was an independent factor affecting the efficacy of PD-1 mAb combined with chemotherapy. ROC curve analysis showed that the area under the curve (AUC) for CD4?/CD8? T cell ratio variation was 0.820 (> 0.5), with a cut-off value of 0.15. Patients with a the CD4+/CD8+ T cell ratio increase of ≥ 0.15 had a longer PFS. Conclusion: The proportion of CD4+ T cells, CD8+ T cells, and the CD4+/CD8+ T cell ratio in peripheral blood can predict the efficacy and prognosis of PD-1 mAb combined with chemotherapy in advanced NSCLC patients.
[Abstract] Objective: To explore the value of lymphocyte subsets in predicting the efficacy and prognosis of non-small cell lung cancer (NSCLC) patients receiving programmed death receptor 1 (PD-1) monoclonal antibody (mAb) combined with chemotherapy. Methods: A retrospective analysis was conducted on the clinical data of 50 NSCLC patients diagnosed and treated with PD-1 mAb combined with chemotherapy at the Second Hospital of Lanzhou University from January 2022 to December 2023. Peripheral blood lymphocyte subsets (including total T cells, CD4+ T cells, CD8+ T cells, NK cells, total B lymphocytes, and CD4+ /CD8+ T cell ratio) were collected before and after two cycles of treatment. After two cycles of treatment, imaging examination was performed to evaluate the therapeutic efficacy, dividing patients into disease control (DC) group and disease progression (PD) group. The relationship between lymphocyte subset levels and the short-term efficacy in NSCLC patients was analyzed using chi-square test, rank sum test, and Logistic regression analysis. The value of lymphocyte subsets in predicting patients’ progression-free survival (PFS) was explored using KaplanMeier method. Results: PD-1 mAb combined with chemotherapy significantly influenced the immune status of NSCLC patients. After treatment, the peripheral blood CD4+ T cells and CD4+ /CD8+ T cell ratio significantly increased (both P < 0.01), while the level of CD8+ T cells decreased. In terms of short-term efficacy, the proportion of CD4+ T cells and the CD4+ /CD8+ T cell ratio in the DC group were significantly higher than those in the PD group (both P < 0.01). Logistic multivariate analysis showed that the CD4+ /CD8+ T cell ratio was an independent factor affecting the efficacy of PD-1 mAb combined with chemotherapy. ROC curve analysis showed that the area under the curve (AUC) for CD4?/CD8? T cell ratio variation was 0.820 (> 0.5), with a cut-off value of 0.15. Patients with a the CD4+/CD8+ T cell ratio increase of ≥ 0.15 had a longer PFS. Conclusion: The proportion of CD4+ T cells, CD8+ T cells, and the CD4+/CD8+ T cell ratio in peripheral blood can predict the efficacy and prognosis of PD-1 mAb combined with chemotherapy in advanced NSCLC patients.
2025, 32(1):79-84.
DOI: 10.3872/j.issn.1007-385X.2025.01.011
Abstract:
[Abstract] Objective: To investigate the value of iSEND (inhaled, self-immunoregulatory, extracellular nanovesicle-based delivery) immune score combined with lung immune prognostic index (LIPI) in evaluating the prognosis of non-small cell lung cancer (NSCLC) patients undergoing immunotherapy. Methods: A retrospective analysis was conducted on the clinical data of 100 patients with advanced NSCLC who received immunotherapy from February 2018 to February 2023. The iSEND immune score and LIPI data of these patients were collected. Patients were divided into 3 groups (poor, moderate, and good) according to their iSEND and LIPI scores. Kaplan-Meier survival curves were polotted to analyze progression-free survival (PFS) among all patients and within different groups. Cox regression analysis was used to identify the risk factors affecting patient prognosis. Results: After immunotherapy, the objective response rate (ORR) was 42.00% (42/100) and the disease control rate (DCR) was 82.00% (82/100) among NSCLC patients. The ORR and DCR were lowest in the poor groups and highest in the good groups for both iSEND immune score and LIPI score, with significant differences among groups (all P < 0.01). The mPFS for all 100 NSCLC patients was 7.63 month (95% CI [7.23, 8.05]). The mPFS for the poor, moderate, and good groups in terms of iSEND immune score was 4.69, 6.58, and 8.99 months, respectively, with the good group having the longest PFS, followed by the moderate group, and the poor group (χ2 = 125.391, P < 0.000 1). Similarly, the mPFS for the poor, moderate, and good groups in terms of LIPI was 4.54, 6.39, and 8.49 months, respectively, with the good group having the longest PFS, followed by the moderate group and poor group (χ2 = 115.707, P < 0.000 1). Cox multivariate analysis identified ECOG PS > 1, distant metastasis, iSEND immune score ≥ 2, and LIPI ≥ 2 as independent risk factors affecting patient prognosis. Conclusion: iSEND immune score and LIPI can serve as valuable prognostic indicators for NSCLC patients undergoing immunotherapy, demonstrating certain clinical value.
[Abstract] Objective: To investigate the value of iSEND (inhaled, self-immunoregulatory, extracellular nanovesicle-based delivery) immune score combined with lung immune prognostic index (LIPI) in evaluating the prognosis of non-small cell lung cancer (NSCLC) patients undergoing immunotherapy. Methods: A retrospective analysis was conducted on the clinical data of 100 patients with advanced NSCLC who received immunotherapy from February 2018 to February 2023. The iSEND immune score and LIPI data of these patients were collected. Patients were divided into 3 groups (poor, moderate, and good) according to their iSEND and LIPI scores. Kaplan-Meier survival curves were polotted to analyze progression-free survival (PFS) among all patients and within different groups. Cox regression analysis was used to identify the risk factors affecting patient prognosis. Results: After immunotherapy, the objective response rate (ORR) was 42.00% (42/100) and the disease control rate (DCR) was 82.00% (82/100) among NSCLC patients. The ORR and DCR were lowest in the poor groups and highest in the good groups for both iSEND immune score and LIPI score, with significant differences among groups (all P < 0.01). The mPFS for all 100 NSCLC patients was 7.63 month (95% CI [7.23, 8.05]). The mPFS for the poor, moderate, and good groups in terms of iSEND immune score was 4.69, 6.58, and 8.99 months, respectively, with the good group having the longest PFS, followed by the moderate group, and the poor group (χ2 = 125.391, P < 0.000 1). Similarly, the mPFS for the poor, moderate, and good groups in terms of LIPI was 4.54, 6.39, and 8.49 months, respectively, with the good group having the longest PFS, followed by the moderate group and poor group (χ2 = 115.707, P < 0.000 1). Cox multivariate analysis identified ECOG PS > 1, distant metastasis, iSEND immune score ≥ 2, and LIPI ≥ 2 as independent risk factors affecting patient prognosis. Conclusion: iSEND immune score and LIPI can serve as valuable prognostic indicators for NSCLC patients undergoing immunotherapy, demonstrating certain clinical value.
2025, 32(1):85-93.
DOI: 10.3872/j.issn.1007-385X.2025.01.012
Abstract:
[摘 要] 肿瘤转移是复杂的动态过程，具有器官选择性，其中肺是常见的转移部位。肺转移与肿瘤患者预后不良密切相关，因 此，研究肿瘤肺转移前微环境（PMN）的特征和机制对于改善患者的预后至关重要。研究表明，原发肿瘤能驯化PMN的形成以促 进肿瘤细胞的转移与定植，甚至决定肿瘤转移的器官选择性。在肺部，原发肿瘤来源的分泌因子与基质细胞、免疫细胞等之间的 相互作用为肿瘤细胞的定植创造了有利条件，形成了以基质重塑、免疫抑制、血管生成及通透性增加、代谢重编程为主要特征的 肺PMN。本综述聚焦于肺PMN的形成因素及其促转移机制，探讨了靶向肺PMN在肿瘤转移预测、诊断或治疗中的潜在应用，为 肿瘤治疗提供了新策略。
[摘 要] 肿瘤转移是复杂的动态过程，具有器官选择性，其中肺是常见的转移部位。肺转移与肿瘤患者预后不良密切相关，因 此，研究肿瘤肺转移前微环境（PMN）的特征和机制对于改善患者的预后至关重要。研究表明，原发肿瘤能驯化PMN的形成以促 进肿瘤细胞的转移与定植，甚至决定肿瘤转移的器官选择性。在肺部，原发肿瘤来源的分泌因子与基质细胞、免疫细胞等之间的 相互作用为肿瘤细胞的定植创造了有利条件，形成了以基质重塑、免疫抑制、血管生成及通透性增加、代谢重编程为主要特征的 肺PMN。本综述聚焦于肺PMN的形成因素及其促转移机制，探讨了靶向肺PMN在肿瘤转移预测、诊断或治疗中的潜在应用，为 肿瘤治疗提供了新策略。
2025, 32(1):94-100.
DOI: 10.3872/j.issn.1007-385X.2025.01.013
Abstract:
[摘 要] 肿瘤免疫治疗已成为肿瘤的晚期治疗、辅助治疗和新辅助治疗的重要组成部分，它彻底革新了传统的肿瘤治疗模 式。然而，大多数肿瘤患者难以获得长期的免疫治疗反应，这突显了探究T淋巴细胞，尤其是CD8+ T细胞在免疫治疗中与肿瘤细 胞的相互作用的重要性。在过去十年中，单细胞测序技术的应用为深入解析肿瘤微环境（TME）中T细胞的作用和功能提供了新 的手段。本文主要综述TME中CD8+ T细胞的异质性特征，深入探讨其在抗肿瘤过程中的状态变化，特别是与时间和空间因素相 关的功能耗竭过程；分析肿瘤中CD8+ T细胞功能障碍的机制，阐述CD8+ T细胞与免疫治疗反应之间的关系，并探索抗肿瘤治疗 中新的有效手段；同时，提出一些关键的未解问题和未来的研究方向，为设计更精准、更有效的肿瘤治疗策略提供参考和指导。
[摘 要] 肿瘤免疫治疗已成为肿瘤的晚期治疗、辅助治疗和新辅助治疗的重要组成部分，它彻底革新了传统的肿瘤治疗模 式。然而，大多数肿瘤患者难以获得长期的免疫治疗反应，这突显了探究T淋巴细胞，尤其是CD8+ T细胞在免疫治疗中与肿瘤细 胞的相互作用的重要性。在过去十年中，单细胞测序技术的应用为深入解析肿瘤微环境（TME）中T细胞的作用和功能提供了新 的手段。本文主要综述TME中CD8+ T细胞的异质性特征，深入探讨其在抗肿瘤过程中的状态变化，特别是与时间和空间因素相 关的功能耗竭过程；分析肿瘤中CD8+ T细胞功能障碍的机制，阐述CD8+ T细胞与免疫治疗反应之间的关系，并探索抗肿瘤治疗 中新的有效手段；同时，提出一些关键的未解问题和未来的研究方向，为设计更精准、更有效的肿瘤治疗策略提供参考和指导。
14 Research progress on the role and molecular mechanism of CHPF in epithelialderived malignant tumor
2025, 32(1):101-106.
DOI: 10.3872/j.issn.1007-385X.2025.01.014
Abstract:
[摘 要] 上皮源性恶性肿瘤是一种起源于上皮组织的恶性疾病，已成为全球健康领域的一大威胁。软骨素聚合因子（CHPF） 是一种新近发现的关键分子，在硫酸软骨素（CS）的生物合成过程中扮演着至关重要的角色，并在多种上皮源性恶性肿瘤组织中 表达升高。CHPF在上皮源性恶性肿瘤中主要通过直接作用发挥其功能，包括调控细胞增殖、促进肿瘤转移，参与多个信号转导 通路，进而影响细胞的功能。此外，CHPF 还可以通过 CS 及其衍生物间接干扰肿瘤微环境（TME）及肿瘤转移。这些机制使 CHPF在肿瘤的多重调控过程中发挥关键作用。本文综合评述了CHPF在上皮源性恶性肿瘤中的作用及其分子机制的最新研究 进展，为未来的研究工作、临床诊断和治疗策略提供了参考和指导。
[摘 要] 上皮源性恶性肿瘤是一种起源于上皮组织的恶性疾病，已成为全球健康领域的一大威胁。软骨素聚合因子（CHPF） 是一种新近发现的关键分子，在硫酸软骨素（CS）的生物合成过程中扮演着至关重要的角色，并在多种上皮源性恶性肿瘤组织中 表达升高。CHPF在上皮源性恶性肿瘤中主要通过直接作用发挥其功能，包括调控细胞增殖、促进肿瘤转移，参与多个信号转导 通路，进而影响细胞的功能。此外，CHPF 还可以通过 CS 及其衍生物间接干扰肿瘤微环境（TME）及肿瘤转移。这些机制使 CHPF在肿瘤的多重调控过程中发挥关键作用。本文综合评述了CHPF在上皮源性恶性肿瘤中的作用及其分子机制的最新研究 进展，为未来的研究工作、临床诊断和治疗策略提供了参考和指导。
2025, 32(1):107-114.
DOI: 10.3872/j.issn.1007-385X.2025.01.015
Abstract:
[摘 要] 肿瘤相关高内皮微静脉（TA-HEV）是肿瘤组织中的一种特殊血管，作为连接血液系统与肿瘤微环境（TME）之间的通 道之一，具有招募免疫细胞（如CD3+ 、CD8+ T细胞和CD20+ B细胞）浸润肿瘤的重要作用，参与杀伤肿瘤细胞的过程。TA-HEV不 仅促进三级淋巴结构（TLS）的形成，而且是成熟TLS的组成部分，二者在多数情况下共定位，在抗肿瘤免疫反应中发挥协同作 用。肿瘤内高密度成熟TA-HEV与多种肿瘤类型患者的良好预后相关，因此TA-HEV在评估肿瘤患者预后中具有潜在价值并可 作为预后标志物。近年来，针对TA-HEV的靶向治疗研究取得了进展，包括MECA-79-紫杉醇-纳米颗粒靶向系统、TA-HEV诱 导剂与免疫检查点抑制剂（ICI）和抗血管生成药物的联合使用，这些策略有望提高肿瘤治疗效果并改善患者的预后和生活质量。
[摘 要] 肿瘤相关高内皮微静脉（TA-HEV）是肿瘤组织中的一种特殊血管，作为连接血液系统与肿瘤微环境（TME）之间的通 道之一，具有招募免疫细胞（如CD3+ 、CD8+ T细胞和CD20+ B细胞）浸润肿瘤的重要作用，参与杀伤肿瘤细胞的过程。TA-HEV不 仅促进三级淋巴结构（TLS）的形成，而且是成熟TLS的组成部分，二者在多数情况下共定位，在抗肿瘤免疫反应中发挥协同作 用。肿瘤内高密度成熟TA-HEV与多种肿瘤类型患者的良好预后相关，因此TA-HEV在评估肿瘤患者预后中具有潜在价值并可 作为预后标志物。近年来，针对TA-HEV的靶向治疗研究取得了进展，包括MECA-79-紫杉醇-纳米颗粒靶向系统、TA-HEV诱 导剂与免疫检查点抑制剂（ICI）和抗血管生成药物的联合使用，这些策略有望提高肿瘤治疗效果并改善患者的预后和生活质量。
2025, 32(1):115-118.
DOI: 10.3872/j.issn.1007-385X.2025.01.016
Abstract:
[摘 要] 铂耐药性卵巢癌（PROC）是卵巢癌进展的必经阶段，患者预后普遍较差。目前常规的治疗方法效果不佳，亟需新的治 疗药物。本文报道1例经多线治疗后进展的PROC患者，在临床试验中接受靶向间皮素（MSLN）的新型抗体偶联药物（ADC） RC88治疗后，肝转移灶和肝门部淋巴结明显缩小，骨转移灶范围减小，达到部分缓解。通过总结该患者的病史资料、影像学表 现、基因检测、治疗方案、治疗效果等病例资料，并对PROC的治疗方法进行文献回顾，探讨RC88治疗作为新药在PROC的应用 前景。靶向MSLN的RC88在PROC治疗中显示出良好的抗肿瘤效果和安全性，能够显著减轻肿瘤负荷，为晚期PROC的治疗带 来了新希望。
[摘 要] 铂耐药性卵巢癌（PROC）是卵巢癌进展的必经阶段，患者预后普遍较差。目前常规的治疗方法效果不佳，亟需新的治 疗药物。本文报道1例经多线治疗后进展的PROC患者，在临床试验中接受靶向间皮素（MSLN）的新型抗体偶联药物（ADC） RC88治疗后，肝转移灶和肝门部淋巴结明显缩小，骨转移灶范围减小，达到部分缓解。通过总结该患者的病史资料、影像学表 现、基因检测、治疗方案、治疗效果等病例资料，并对PROC的治疗方法进行文献回顾，探讨RC88治疗作为新药在PROC的应用 前景。靶向MSLN的RC88在PROC治疗中显示出良好的抗肿瘤效果和安全性，能够显著减轻肿瘤负荷，为晚期PROC的治疗带 来了新希望。
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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.