BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blocka...BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.展开更多
To improve the efficacy of lenvatinib in combination with programmed death-1(PD-1)blockade therapy for hepatocellular carcinoma(HCC),we screened the suppressive metabolic enzymes that sensitize HCC to lenvatinib and P...To improve the efficacy of lenvatinib in combination with programmed death-1(PD-1)blockade therapy for hepatocellular carcinoma(HCC),we screened the suppressive metabolic enzymes that sensitize HCC to lenvatinib and PD-1 blockade,thus impeding HCC progression.After analysis of the CRISPR‒Cas9 screen,phosphatidylinositol-glycan biosynthesis class L(PIGL)ranked first in the positive selection list.PIGL depletion had no effect on tumor cell growth in vitro but reprogrammed the tumor microenvironment(TME)in vivo to support tumor cell survival.Specifically,nuclear PIGL disrupted the interaction between cMyc/BRD4 on the distant promoter of target genes and thus decreased the expression of CCL2 and CCL20,which are involved in shaping the immunosuppressive TME by recruiting macrophages and regulatory T cells.PIGL phosphorylation at Y81 by FGFR2 abolished the interaction of PIGL with importinα/β1,thus retaining PIGL in the cytosol and facilitating tumor evasion by releasing CCL2 and CCL20.Clinically,elevated nuclear PIGL predicts a better prognosis for HCC patients and presents a positive correlation with CD8+T-cell enrichment in tumors.Clinically,our findings highlight that the nuclear PIGL intensity or the change in PIGL-Y81 phosphorylation should be used as a biomarker to guide lenvatinib with PD-1 blockade therapy.展开更多
As a common tumor of the urinary system,the morbidity and mortality related to renal carcinoma,are increasing annually.Clear cell renal cell carcinoma(CCRCC)is the most common subtype of renal cell carcinoma,accountin...As a common tumor of the urinary system,the morbidity and mortality related to renal carcinoma,are increasing annually.Clear cell renal cell carcinoma(CCRCC)is the most common subtype of renal cell carcinoma,accounting for approximately 75%of the total number of patients with renal cell carcinoma.Currently,the clinical treatment of ccRCC involves targeted therapy,immunotherapy,and a combination of the two.In immunotherapy,PD-1/PD-L1 blocking of activated T cells to kill cancer cells is the most common treatment.However,as treatment progresses,some patients gradually develop resistance to immunotherapy.Meanwhile,other patients experience great side effects after immunotherapy,resulting in a survival status far lower than the expected survival rate.Based on these clinical problems,many researchers have been working on the improvement of tumor immunotherapy in recent years and have accumulated numerous research results.We hope to find a more suitable direction for future immunotherapy for ccRCC by combining these results and the latest research progress.展开更多
目的探究真实世界中程序性死亡蛋白1(Programmed Death Protein 1,PD-1)/程序性死亡蛋白配体1(Programmed Death Protein Ligand 1,PD-L1)抑制剂治疗对晚期非小细胞肺癌(Non-Small Cell Lung Cancer,NSCLC)二线及以上患者预后转归的影...目的探究真实世界中程序性死亡蛋白1(Programmed Death Protein 1,PD-1)/程序性死亡蛋白配体1(Programmed Death Protein Ligand 1,PD-L1)抑制剂治疗对晚期非小细胞肺癌(Non-Small Cell Lung Cancer,NSCLC)二线及以上患者预后转归的影响。方法选取2019年1月—2023年7月涟水县人民医院就诊的112例晚期NSCLC二线及以上患者为研究对象,依据治疗方法分为两组,每组56例,对照组接受二线及以上单药化疗,观察组接受PD-1/PD-L1抑制剂免疫治疗,对比两组生存质量、无进展生存期、总生存期及不良反应发生率。结果化疗4个周期后,观察组生存质量评分显著高于对照组,差异有统计学意义(P<0.05)。观察组无进展生存期、总生存期显著优于对照组,差异有统计学意义(P均<0.05)。观察组不良反应发生率显著低于对照组,且观察组高血压发生人数显著少于对照组,差异有统计学意义(P均<0.05)。结论晚期NSCLC患者二线治疗中PD-1/PD-L1抑制剂免疫治疗能提升患者生存质量,降低其不良反应发生率。展开更多
PD-1 blockade has demonstrated impressive clinical outcomes in colorectal cancers that have high microsatellite instability.However,the therapeutic efficacy for patients with tumors with low microsatellite instability...PD-1 blockade has demonstrated impressive clinical outcomes in colorectal cancers that have high microsatellite instability.However,the therapeutic efficacy for patients with tumors with low microsatellite instability or stable microsatellites needs further improvement.Here,we have demonstrated that low-dose decitabine could increase the expression of immune-related genes such as major histocompatibility complex genes and cytokine-related genes as well as the number of lymphocytes at the tumor site in CT26 colorectal cancer-bearing mice.A more significant inhibition of tumor growth and a prolongation of survival were observed in the CT26 mouse model after treatment with a combination of PD-1 blockade and decitabine than in mice treated with decitabine or PD-1 blockade alone.The anti-tumor effect of the PD-1 blockade was enhanced by low-dose decitabine.The results of RNA sequencing and whole-genome bisulfite sequencing of decitabine-treated CT26 cells and tumor samples with microsatellite stability from the patient tumor-derived xenograft model have shown that many immune-related genes,including antigen-processing and antigen-presenting genes,were upregulated,whereas the promoter demethylation was downregulated after decitabine exposure.Therefore,decitabine-based tumor microenvironment re-modulation could improve the effect of the PD-1 blockade.The application of decitabine in PD-1 blockade-based immunotherapy may elicit more potent immune responses,which can provide clinical benefits to the colorectal cancer patients with low microsatellite instability or stable microsatellites.展开更多
基金Supported by Shaoxing Health Science and Technology Program,No.2022SY016,No.2022KY010.
文摘BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.
基金supported mainly by the Guangdong Natural Science Foundation of Guangdong Province of China 2021B1515020016in part by NSFC grants No.82000616,82272714,82173149Science and Technology Program of Guangdong Province No.2020B1212060019.
文摘To improve the efficacy of lenvatinib in combination with programmed death-1(PD-1)blockade therapy for hepatocellular carcinoma(HCC),we screened the suppressive metabolic enzymes that sensitize HCC to lenvatinib and PD-1 blockade,thus impeding HCC progression.After analysis of the CRISPR‒Cas9 screen,phosphatidylinositol-glycan biosynthesis class L(PIGL)ranked first in the positive selection list.PIGL depletion had no effect on tumor cell growth in vitro but reprogrammed the tumor microenvironment(TME)in vivo to support tumor cell survival.Specifically,nuclear PIGL disrupted the interaction between cMyc/BRD4 on the distant promoter of target genes and thus decreased the expression of CCL2 and CCL20,which are involved in shaping the immunosuppressive TME by recruiting macrophages and regulatory T cells.PIGL phosphorylation at Y81 by FGFR2 abolished the interaction of PIGL with importinα/β1,thus retaining PIGL in the cytosol and facilitating tumor evasion by releasing CCL2 and CCL20.Clinically,elevated nuclear PIGL predicts a better prognosis for HCC patients and presents a positive correlation with CD8+T-cell enrichment in tumors.Clinically,our findings highlight that the nuclear PIGL intensity or the change in PIGL-Y81 phosphorylation should be used as a biomarker to guide lenvatinib with PD-1 blockade therapy.
基金The Ph.D.Start-Up Fund of Liaoning Province from GW(2021-BS-209,Liaoning Province,30000 CNY)Natural Science Foundation of Liaoning Province of China(2021-MS-278,Liaoning Province,100000 CNY).
文摘As a common tumor of the urinary system,the morbidity and mortality related to renal carcinoma,are increasing annually.Clear cell renal cell carcinoma(CCRCC)is the most common subtype of renal cell carcinoma,accounting for approximately 75%of the total number of patients with renal cell carcinoma.Currently,the clinical treatment of ccRCC involves targeted therapy,immunotherapy,and a combination of the two.In immunotherapy,PD-1/PD-L1 blocking of activated T cells to kill cancer cells is the most common treatment.However,as treatment progresses,some patients gradually develop resistance to immunotherapy.Meanwhile,other patients experience great side effects after immunotherapy,resulting in a survival status far lower than the expected survival rate.Based on these clinical problems,many researchers have been working on the improvement of tumor immunotherapy in recent years and have accumulated numerous research results.We hope to find a more suitable direction for future immunotherapy for ccRCC by combining these results and the latest research progress.
文摘目的探究真实世界中程序性死亡蛋白1(Programmed Death Protein 1,PD-1)/程序性死亡蛋白配体1(Programmed Death Protein Ligand 1,PD-L1)抑制剂治疗对晚期非小细胞肺癌(Non-Small Cell Lung Cancer,NSCLC)二线及以上患者预后转归的影响。方法选取2019年1月—2023年7月涟水县人民医院就诊的112例晚期NSCLC二线及以上患者为研究对象,依据治疗方法分为两组,每组56例,对照组接受二线及以上单药化疗,观察组接受PD-1/PD-L1抑制剂免疫治疗,对比两组生存质量、无进展生存期、总生存期及不良反应发生率。结果化疗4个周期后,观察组生存质量评分显著高于对照组,差异有统计学意义(P<0.05)。观察组无进展生存期、总生存期显著优于对照组,差异有统计学意义(P均<0.05)。观察组不良反应发生率显著低于对照组,且观察组高血压发生人数显著少于对照组,差异有统计学意义(P均<0.05)。结论晚期NSCLC患者二线治疗中PD-1/PD-L1抑制剂免疫治疗能提升患者生存质量,降低其不良反应发生率。
基金This work was supported by grants from the National Key R&D Program of China(2016YFC1303504)the National Natural Science Foundation of China(81471625 and 81671644).
文摘PD-1 blockade has demonstrated impressive clinical outcomes in colorectal cancers that have high microsatellite instability.However,the therapeutic efficacy for patients with tumors with low microsatellite instability or stable microsatellites needs further improvement.Here,we have demonstrated that low-dose decitabine could increase the expression of immune-related genes such as major histocompatibility complex genes and cytokine-related genes as well as the number of lymphocytes at the tumor site in CT26 colorectal cancer-bearing mice.A more significant inhibition of tumor growth and a prolongation of survival were observed in the CT26 mouse model after treatment with a combination of PD-1 blockade and decitabine than in mice treated with decitabine or PD-1 blockade alone.The anti-tumor effect of the PD-1 blockade was enhanced by low-dose decitabine.The results of RNA sequencing and whole-genome bisulfite sequencing of decitabine-treated CT26 cells and tumor samples with microsatellite stability from the patient tumor-derived xenograft model have shown that many immune-related genes,including antigen-processing and antigen-presenting genes,were upregulated,whereas the promoter demethylation was downregulated after decitabine exposure.Therefore,decitabine-based tumor microenvironment re-modulation could improve the effect of the PD-1 blockade.The application of decitabine in PD-1 blockade-based immunotherapy may elicit more potent immune responses,which can provide clinical benefits to the colorectal cancer patients with low microsatellite instability or stable microsatellites.
