BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and com...BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective immunotherapy.AIM To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer models.METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 group.Tumor-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were evaluated.Real-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of time.The growth curves of tumors were drawn.RESULTS The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control group.Additionally,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA expression.Tumor volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic effect.CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer.展开更多
Background:Previous experiments have demonstrated that hypofractionated radiation therapy(HFRT),low-dose radiation therapy(LDRT),and combined anti-programmed cell death protein 1(αPD-1)can enhance the abscopal effect...Background:Previous experiments have demonstrated that hypofractionated radiation therapy(HFRT),low-dose radiation therapy(LDRT),and combined anti-programmed cell death protein 1(αPD-1)can enhance the abscopal effect.Combined with the phenomenon of low prognosis in patients with breast cancer lung metastasis,our study establishes a mouse model and changes the irradiation regimen of LDRT to explore its preventive effect on breast cancer lung metastasis.Methods:The breast cancer subcutaneous graft tumor model was developed.Two-lung prophylactic LDRT was performed prior to the onset of lung metastases,in combination with HFRT(8 Gy,3f),andαPD-1(200μg,4f)therapy.We watched and documented the tumor volume,survival duration,and number of lung metastases.Furthermore,after labeling the corresponding cells using markers,we detected immune-related cell infiltration by immunohistochemistry and flow cytometry,such as T cells.We also determined the expression of cytokines(IFN-γand TNF-α)by enzyme-linked immunosorbent assay.Result:The triple therapy(HFRT+LDRT+αPD-1)resulted in tumor shrinkage and prolonged survival in mice,with median survival extending from 35 to 52 days.The most notable decrease in the quantity of advanced lung metastatic nodules in breast cancer was observed with the triple therapy(HFRT+LDRT+αPD-1)(p<0.05).Furthermore,according to immunohistochemistry and flow cytometry,the triple treatment(HFRT+LDRT+αPD-1)showed the greatest expression of CD8^(+)T cells.Additionally,the ratio of CD8^(+)/CD4^(+)T cells was considerably greater than that of the groups(p<0.0001).Triple therapy(HFRT+LDRT+αPD-1)increased the recruitment of DCs cells,promoted IFN-γand TNF-αexpression,and curbed the aggregation of MDSCs cells(p<0.05).Conclusion:Prophylactic LDRT to the lungs,based on HFRT andαPD-1,can enhance anti-tumor efficacy and prevent advanced lung metastases from breast cancer.The process involves boosting the recruitment of DCs and CD8^(+)T cells,preventing MDSC cell aggregation,and lessening the tumor microenvironment’s immunosuppressive effects.展开更多
BACKGROUND Colorectal cancer(CRC)is the third most prevalent form of cancer worldwide.Among patients with CRC,colorectal liver metastasis(CRLM)is the foremost direct contributor to mortality.In recent years,immunother...BACKGROUND Colorectal cancer(CRC)is the third most prevalent form of cancer worldwide.Among patients with CRC,colorectal liver metastasis(CRLM)is the foremost direct contributor to mortality.In recent years,immunotherapy has swiftly risen to prominence as a vital approach for treating a range of solid tumors,including CRC.We present a unique case of a patient suffering from CRLM,with the goal of offering an insightful example and relevant references for the treatment of CRLM.CASE SUMMARY We report a patient who experienced liver metastasis after undergoing successful surgical removal of CRC,with the postoperative pathological stage identified as pT4N2aM0.The patient has been receiving a combination treatment of Western and Traditional Chinese Medicine.Regular assessments of the patient’s condition have been conducted,encompassing evaluations of serum carcinoembryonic antigen levels,carbohydrate antigen 199,and observations of the tongue complexion and its coating.The patient achieved clinical remission after anti-programmed death-1 immunotherapy when various systemic therapies failed.Since the diagnosis of CRLM,the patient has survived for more than 6 years,surpassing the expected survival time for those with advanced CRC.CONCLUSION This case illustrates the considerable promise of anti-programmed death-1 immunotherapy in managing CRLM,especially in scenarios of drug resistance and disease progression.展开更多
BACKGROUND Patients with microsatellite stable(MSS)metastatic colorectal cancer(mCRC)typically exhibit an immunosuppressive tumor microenvironment and demonstrate a low response rate to immunotherapy.Reports suggest t...BACKGROUND Patients with microsatellite stable(MSS)metastatic colorectal cancer(mCRC)typically exhibit an immunosuppressive tumor microenvironment and demonstrate a low response rate to immunotherapy.Reports suggest that chemotherapy and anti-angiogenic therapy may have the potential to enhance the response to immunotherapy in these patients.This study aims to evaluate the effectiveness and safety of chemotherapy combined with bevacizumab with or without antiprogrammed death 1(PD-1)immunotherapy as the second-line regimen for MSS mCRC.AIM To evaluate the effectiveness and safety of chemotherapy combined with bevacizumab with or without anti-PD-1 immunotherapy as the second-line regimen for MSS mCRC.METHODS A retrospective analysis was conducted on patients with MSS mCRC diagnosed at Peking University First Hospital and Jilin Cancer Hospital from January 2020 to December 2024.The patients were divided into two groups:The experimental group receiving second-line chemotherapy combined with bevacizumab and anti-PD-1 immunotherapy,and the control group receiving chemotherapy combined with bevacizumab.Propensity score matching was applied to balance potential prognostic factors,including age,gender,Eastern Cooperative Oncology Group score,number of metastases,and primary tumor site.The progression-free survival,overall survival,disease control rate,objective response rate,and treatment-related adverse reactions were compared between the two groups.Kaplan-Meier analysis and log-rank test were used to compare survival outcomes.Inverse probability of treatment weighting was used for sensitivity analysis.RESULTS Propensity score matching resulted in 103 matched eligible patients.The median follow-up period was 13.9 months in the matched cohort.The objective response rate was 11.5%and 9%for the experimental and control groups,respectively(P=0.710),while the disease control rate was 76.9%and 53.2%,respectively(P=0.058).The median progression-free survival in the experimental group was 8.27 months[95%confidence interval(CI):6.7-14.7 months],significantly higher than that in the control group,which was 4.63 months(95%CI:3.9-5.67 months)(hazard ratio=0.4143,95%CI:0.2462-0.6972,P=0.00066).There was a trend towards the higher median overall survival in the experimental group compared to the control group(hazard ratio=0.4504,95%CI:0.1897-1.07,P=0.064).The incidences of adverse events were similar between the two groups.CONCLUSION Compared with the standard second-line chemotherapy combined with bevacizumab regimen,second-line therapy that combines chemotherapy with bevacizumab and anti-PD-1 immunotherapy has demonstrated promising efficacy in the treatment of MSS mCRC,while exhibiting a similar safety profile.展开更多
BACKGROUND Immune checkpoint inhibitors(ICIs)are a new class of antitumor agents.They enhance antitumor effects by blocking inhibitory receptors and related ligands expressed on T cells.ICIs also modulate regular immu...BACKGROUND Immune checkpoint inhibitors(ICIs)are a new class of antitumor agents.They enhance antitumor effects by blocking inhibitory receptors and related ligands expressed on T cells.ICIs also modulate regular immune cell activity,affecting the immune system and causing immune-related adverse events.The renal system is sometimes affected by these adverse events.Currently,the literature on ICIs-related glomerular injuries is scarce.CASE SUMMARY We present a patient who developed granulomatosis with polyangiitis(GPA)3 weeks after treatment with the anti-programmed cell death-1 inhibitor,tislel-izumab.The patient experienced proteinuria,hematuria,and acute kidney injury without pulmonary hemorrhage and tested positive for anti-neutrophil cyto-plasmic antibody(ANCA)-cytoplasmic type.Renal biopsy confirmed ANCA-associated vasculitis,and GPA was finally diagnosed.The patient received pulse treatment with glucocorticoids and cyclophosphamide,and renal function improved.After self-discontinuation of the drug,the disease recurred,and the original treatment regimen was continued.However,the patient’s renal function continued to deteriorate.CONCLUSION Glucocorticoids plus cyclophosphamide are effective for treating GPA induced by tislelizumab.However,follow-up and patient education are needed.展开更多
目的探索酮还原酶家族1成员C3(aldo-keto reductase family 1 member C3,AKR1C3)对乳腺癌恶性细胞生物学行为的干预作用及对程序性细胞死亡蛋白/程序性死亡-配体1(programmed cell death protein1/programmed death-ligand1,PD-1/PD-L)...目的探索酮还原酶家族1成员C3(aldo-keto reductase family 1 member C3,AKR1C3)对乳腺癌恶性细胞生物学行为的干预作用及对程序性细胞死亡蛋白/程序性死亡-配体1(programmed cell death protein1/programmed death-ligand1,PD-1/PD-L)通路的影响。方法把MCF-7人乳腺癌细胞中NC组和AKR1C3组分别转染空质粒和AKR1C3质粒,采用MTT法检测转染后24 h、48 h、72 h细胞活力;采用流式细胞技术测定各组细胞的存活率以及早期、晚期凋亡比例;通过Transwell实验对各组细胞的迁移和侵袭能力进行检测;通过Western blot检测各组细胞PD-1、PD-L1、蛋白激酶B(protein kinase b,AKT)蛋白表达水平。使用C57BL/6小鼠构建荷瘤模型,将采用人乳腺癌MCF-7细胞转染NC质粒和AKR1C3质粒进行细胞荷瘤,每3 d测量瘤体积,持续21 d,绘制两组小鼠肿瘤生长曲线,并于实验终点测量肿瘤质量。结果相较于NC组,AKR1C3组细胞活力降低(P<0.05),并且具有时间依赖效应(P<0.05),迁移和侵袭能力降低(P<0.05),早期凋亡和晚期凋亡比例升高(P<0.05),PD-1、PD-L1、AKT蛋白表达水平降低(P<0.05)。动物实验表明,AKR1C3组小鼠肿瘤体积降低,肿瘤质量下降(P<0.05)。结论AKR1C3可以抑制人乳腺癌细胞恶性生物学行为,抑制PD-1/PDL1信号通路蛋白表达。展开更多
基金Science and Technology Program of Guangzhou,No.202102010077International Science Foundation of Guangzhou Fuda Cancer Hospital,No.Y2020-ZD-03.
文摘BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective immunotherapy.AIM To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer models.METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 group.Tumor-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were evaluated.Real-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of time.The growth curves of tumors were drawn.RESULTS The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control group.Additionally,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA expression.Tumor volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic effect.CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer.
基金supported by a grant from the Southwest Medical University’s Program for Creating Popular Science Works(No.00160580).
文摘Background:Previous experiments have demonstrated that hypofractionated radiation therapy(HFRT),low-dose radiation therapy(LDRT),and combined anti-programmed cell death protein 1(αPD-1)can enhance the abscopal effect.Combined with the phenomenon of low prognosis in patients with breast cancer lung metastasis,our study establishes a mouse model and changes the irradiation regimen of LDRT to explore its preventive effect on breast cancer lung metastasis.Methods:The breast cancer subcutaneous graft tumor model was developed.Two-lung prophylactic LDRT was performed prior to the onset of lung metastases,in combination with HFRT(8 Gy,3f),andαPD-1(200μg,4f)therapy.We watched and documented the tumor volume,survival duration,and number of lung metastases.Furthermore,after labeling the corresponding cells using markers,we detected immune-related cell infiltration by immunohistochemistry and flow cytometry,such as T cells.We also determined the expression of cytokines(IFN-γand TNF-α)by enzyme-linked immunosorbent assay.Result:The triple therapy(HFRT+LDRT+αPD-1)resulted in tumor shrinkage and prolonged survival in mice,with median survival extending from 35 to 52 days.The most notable decrease in the quantity of advanced lung metastatic nodules in breast cancer was observed with the triple therapy(HFRT+LDRT+αPD-1)(p<0.05).Furthermore,according to immunohistochemistry and flow cytometry,the triple treatment(HFRT+LDRT+αPD-1)showed the greatest expression of CD8^(+)T cells.Additionally,the ratio of CD8^(+)/CD4^(+)T cells was considerably greater than that of the groups(p<0.0001).Triple therapy(HFRT+LDRT+αPD-1)increased the recruitment of DCs cells,promoted IFN-γand TNF-αexpression,and curbed the aggregation of MDSCs cells(p<0.05).Conclusion:Prophylactic LDRT to the lungs,based on HFRT andαPD-1,can enhance anti-tumor efficacy and prevent advanced lung metastases from breast cancer.The process involves boosting the recruitment of DCs and CD8^(+)T cells,preventing MDSC cell aggregation,and lessening the tumor microenvironment’s immunosuppressive effects.
基金Supported by the National Key R and D Program of China,No.2022YFC3500200 and No.2022YFC3500204Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine,No.ZYYCXTD-C-202208+3 种基金NATCM’s Project of Highlevel Construction of Key TCM Disciplines,No.[2023]85Qing Lan Project of Jiangsu Higher Education Institutions,No.[2023]27Jiangsu Postgraduate Practice Innovation Plan,No.SJCX22_0706General Project of Universities’Philosophy and Social Science in Jiangsu Province,No.2024SJYB0564.
文摘BACKGROUND Colorectal cancer(CRC)is the third most prevalent form of cancer worldwide.Among patients with CRC,colorectal liver metastasis(CRLM)is the foremost direct contributor to mortality.In recent years,immunotherapy has swiftly risen to prominence as a vital approach for treating a range of solid tumors,including CRC.We present a unique case of a patient suffering from CRLM,with the goal of offering an insightful example and relevant references for the treatment of CRLM.CASE SUMMARY We report a patient who experienced liver metastasis after undergoing successful surgical removal of CRC,with the postoperative pathological stage identified as pT4N2aM0.The patient has been receiving a combination treatment of Western and Traditional Chinese Medicine.Regular assessments of the patient’s condition have been conducted,encompassing evaluations of serum carcinoembryonic antigen levels,carbohydrate antigen 199,and observations of the tongue complexion and its coating.The patient achieved clinical remission after anti-programmed death-1 immunotherapy when various systemic therapies failed.Since the diagnosis of CRLM,the patient has survived for more than 6 years,surpassing the expected survival time for those with advanced CRC.CONCLUSION This case illustrates the considerable promise of anti-programmed death-1 immunotherapy in managing CRLM,especially in scenarios of drug resistance and disease progression.
基金Supported by the National High Level Hospital Clinical Research Funding(Multi-center Clinical Research Project of Peking University First Hospital),No.2022CR65.
文摘BACKGROUND Patients with microsatellite stable(MSS)metastatic colorectal cancer(mCRC)typically exhibit an immunosuppressive tumor microenvironment and demonstrate a low response rate to immunotherapy.Reports suggest that chemotherapy and anti-angiogenic therapy may have the potential to enhance the response to immunotherapy in these patients.This study aims to evaluate the effectiveness and safety of chemotherapy combined with bevacizumab with or without antiprogrammed death 1(PD-1)immunotherapy as the second-line regimen for MSS mCRC.AIM To evaluate the effectiveness and safety of chemotherapy combined with bevacizumab with or without anti-PD-1 immunotherapy as the second-line regimen for MSS mCRC.METHODS A retrospective analysis was conducted on patients with MSS mCRC diagnosed at Peking University First Hospital and Jilin Cancer Hospital from January 2020 to December 2024.The patients were divided into two groups:The experimental group receiving second-line chemotherapy combined with bevacizumab and anti-PD-1 immunotherapy,and the control group receiving chemotherapy combined with bevacizumab.Propensity score matching was applied to balance potential prognostic factors,including age,gender,Eastern Cooperative Oncology Group score,number of metastases,and primary tumor site.The progression-free survival,overall survival,disease control rate,objective response rate,and treatment-related adverse reactions were compared between the two groups.Kaplan-Meier analysis and log-rank test were used to compare survival outcomes.Inverse probability of treatment weighting was used for sensitivity analysis.RESULTS Propensity score matching resulted in 103 matched eligible patients.The median follow-up period was 13.9 months in the matched cohort.The objective response rate was 11.5%and 9%for the experimental and control groups,respectively(P=0.710),while the disease control rate was 76.9%and 53.2%,respectively(P=0.058).The median progression-free survival in the experimental group was 8.27 months[95%confidence interval(CI):6.7-14.7 months],significantly higher than that in the control group,which was 4.63 months(95%CI:3.9-5.67 months)(hazard ratio=0.4143,95%CI:0.2462-0.6972,P=0.00066).There was a trend towards the higher median overall survival in the experimental group compared to the control group(hazard ratio=0.4504,95%CI:0.1897-1.07,P=0.064).The incidences of adverse events were similar between the two groups.CONCLUSION Compared with the standard second-line chemotherapy combined with bevacizumab regimen,second-line therapy that combines chemotherapy with bevacizumab and anti-PD-1 immunotherapy has demonstrated promising efficacy in the treatment of MSS mCRC,while exhibiting a similar safety profile.
文摘BACKGROUND Immune checkpoint inhibitors(ICIs)are a new class of antitumor agents.They enhance antitumor effects by blocking inhibitory receptors and related ligands expressed on T cells.ICIs also modulate regular immune cell activity,affecting the immune system and causing immune-related adverse events.The renal system is sometimes affected by these adverse events.Currently,the literature on ICIs-related glomerular injuries is scarce.CASE SUMMARY We present a patient who developed granulomatosis with polyangiitis(GPA)3 weeks after treatment with the anti-programmed cell death-1 inhibitor,tislel-izumab.The patient experienced proteinuria,hematuria,and acute kidney injury without pulmonary hemorrhage and tested positive for anti-neutrophil cyto-plasmic antibody(ANCA)-cytoplasmic type.Renal biopsy confirmed ANCA-associated vasculitis,and GPA was finally diagnosed.The patient received pulse treatment with glucocorticoids and cyclophosphamide,and renal function improved.After self-discontinuation of the drug,the disease recurred,and the original treatment regimen was continued.However,the patient’s renal function continued to deteriorate.CONCLUSION Glucocorticoids plus cyclophosphamide are effective for treating GPA induced by tislelizumab.However,follow-up and patient education are needed.
