以往的研究主要集中在肿瘤细胞在免疫逃逸中的变化,而对肿瘤微环境(tumor microenvironment, TME)对免疫逃逸的影响知之甚少。肿瘤相关成纤维细胞(tumor-associated fibroblasts, TAFs)是TME的重要组成部分,具有特殊的生理生化特性,但...以往的研究主要集中在肿瘤细胞在免疫逃逸中的变化,而对肿瘤微环境(tumor microenvironment, TME)对免疫逃逸的影响知之甚少。肿瘤相关成纤维细胞(tumor-associated fibroblasts, TAFs)是TME的重要组成部分,具有特殊的生理生化特性,但其具体机制尚不清楚。为了研究TAF对胃癌细胞PD-L1表达的影响,通过transwell将胃癌细胞株MNK45、SGC7901与TAFs非接触共培养1、3、7 d。采用qRT-PCR和流式细胞仪检测PD-L1 mRNA和蛋白表达。然后选择95例胃癌组织,通过免疫组化检测PD-L1和TAFs的表达。结果显示,实验组PD-L1 mRNA和蛋白表达量均显著高于对照组。胃癌中PD-L1的表达与大量淋巴细胞浸润、弥漫性/混合性组织学和瘤内TAFs有关。综上所述,TAFs通过提高PD-L1的表达促进胃癌细胞株的生长。Previous studies have focused on the changes of tumour cells in immune escape, and less is known about the effect of the tumour microenvironment (TME) on immune escape. Tumour-associated fibroblasts (TAFs) cells are an important part of the TME and have special physiological and biochemical characteristics, but the specific mechanism has not been clarified. In order to investigate the effect of TAFs on the expression of PD-L1 in gastric cancer cells, gastric cancer cell lines MNK45, SGC7901 were non-contact coculturing with TAFs 1, 3 and 7 d via transwell. PD-L1 mRNA and protein expression were detected using qRT-PCR and FCM. Then, 95 cases of gastric cancer tissues were selected and PD-L1 and TAFs expressions were determined by immunohistochemical examination. The results showed that the mRNA and protein expression of PD-L1 in the experiment group were significantly higher than that in the control group. PD-L1 expression was associated with massive lymphocyte infiltration, diffuse/mixed histology and intratumoral TAFs in gastric cancers. In conclusion, TAFs promoted the growth of gastric cancer cell lines by increasing the PD-L1 expression.展开更多
目的评价阿帕替尼联合程序性死亡受体1/程序性死亡受体配体1(PD-1/PD-L1)抑制剂治疗恶性实体瘤的有效性与安全性。方法检索PubMed、Web of Science、Embase、Cochrane Library、中国知网、维普网、万方数据、中国生物医学文献数据库,收...目的评价阿帕替尼联合程序性死亡受体1/程序性死亡受体配体1(PD-1/PD-L1)抑制剂治疗恶性实体瘤的有效性与安全性。方法检索PubMed、Web of Science、Embase、Cochrane Library、中国知网、维普网、万方数据、中国生物医学文献数据库,收集阿帕替尼联合PD-1/PD-L1抑制剂和(或)化疗/其他疗法(联合组)对比阿帕替尼或PD-1/PD-L1抑制剂单药和(或)化疗/其他疗法(对照组)治疗恶性实体瘤的随机对照研究(RCT),检索时限为建库至2025年5月。筛选文献、提取资料、评价文献质量后,采用RevMan 5.3和Stata 14.0软件进行Meta分析。结果共纳入28篇RCTs,包括2974例患者。联合组患者的客观缓解率[RR=1.639,95%CI(1.452,1.851),P<0.00001],疾病控制率[RR=1.284,95%CI(1.178,1.399),P<0.00001],CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)以及高血压、疲劳乏力、蛋白尿、血小板减少等不良反应的发生率均显著高于对照组(P<0.05或P<0.00001);疾病进展率[RR=0.497,95%CI(0.437,0.566),P<0.00001]、血清肿瘤标志物水平、CD8^(+)均显著低于对照组(P<0.05或P<0.00001)。不同类型肿瘤的亚组分析结果显示,联合组患者的客观缓解率和疾病控制率均显著高于对照组(P<0.05)。敏感性分析结果显示,本研究结果的稳定性良好。发表偏倚分析结果显示,本研究存在发表偏倚的可能性较大。结论阿帕替尼联合PD-1/PD-L1抑制剂治疗不同类型肿瘤的疗效显著,但需注意高血压、疲劳乏力、蛋白尿、血小板减少的发生。展开更多
放疗与以免疫检查点抑制剂(如PD-1/PD-L1抑制剂)为主的免疫治疗,是实体瘤治疗的关键手段。本文聚焦放疗的免疫调节效应与二者联合应用,阐述放疗对正向免疫调节的作用机制、放疗与PD-1/PD-L1抑制剂联合时对肿瘤免疫微环境影响,远隔效应...放疗与以免疫检查点抑制剂(如PD-1/PD-L1抑制剂)为主的免疫治疗,是实体瘤治疗的关键手段。本文聚焦放疗的免疫调节效应与二者联合应用,阐述放疗对正向免疫调节的作用机制、放疗与PD-1/PD-L1抑制剂联合时对肿瘤免疫微环境影响,远隔效应的发生等。相关临床试验显示,该联合治疗在非小细胞肺癌、肝细胞癌等多种实体瘤中展现出良好效果,但不同癌种获益有别。目前,联合治疗的最佳剂量、分割方案及时间安排策略尚存争议,需依据肿瘤类型和治疗目标进行个体化调整。本文系统梳理现有研究,为放疗与PD-1/PD-L1抑制剂联合治疗的临床实践提供全面科学依据与实用参考。Radiotherapy and immunotherapy mainly based on immune checkpoint inhibitors (such as PD-1/PD-L1 inhibitors) are key approaches for the treatment of solid tumors. This article focuses on the immunomodulatory effects of radiotherapy and their combined application. It elaborates on the mechanisms of radiotherapy’s positive immunomodulation, the impact of the combination of radiotherapy and PD-1/PD-L1 inhibitors on the tumor immune microenvironment, and the occurrence of the abscopal effect. Relevant clinical trials have demonstrated that this combined treatment has shown good efficacy in various solid tumors such as non-small cell lung cancer and hepatocellular carcinoma, yet the benefits vary among different cancer types. Currently, there are still controversies regarding the optimal dose, fractionation scheme, and timing strategy of the combined treatment, which need to be adjusted individually according to the tumor type and treatment goals. This article systematically reviews the existing research, providing a comprehensive scientific basis and practical reference for the clinical practice of the combined treatment of radiotherapy and PD-1/PD-L1 inhibitors.展开更多
目的系统评价复方苦参注射液联合程序性死亡受体1(programmed death receptor 1,PD-1)/程序性死亡配体1(programmed death ligand 1,PD-L1)抑制剂治疗非小细胞肺癌的临床疗效及安全性。方法文献检索限定时间为从建库至2025年6月23日,在...目的系统评价复方苦参注射液联合程序性死亡受体1(programmed death receptor 1,PD-1)/程序性死亡配体1(programmed death ligand 1,PD-L1)抑制剂治疗非小细胞肺癌的临床疗效及安全性。方法文献检索限定时间为从建库至2025年6月23日,在计算机检索PubMed、Embase、Cochrane library、知网、维普、万方和中国生物医学文献数据库关于复方苦参注射液联合PD-1/PD-L1抑制剂治疗非小细胞肺癌的随机对照试验。根据纳排标准筛选文献后,采用Cochrane偏倚风险评估工具进行质量评价,使用Revman 5.4进行统计学分析。结果共纳入6篇文献,包含患者520例。Meta分析结果显示:在临床疗效方面,相比于PD-1/PD-L1抑制剂治疗方案组,复方苦参注射液联合PD-1/PD-L1抑制剂治疗方案组能有效改善客观缓解率(RR=1.66,95%CI:1.36~2.03,P<0.001)、疾病控制率(RR=1.24,95%CI:1.08~1.42,P=0.002)和卡氏功能状态评分(MD=5.66,95%CI:2.22~9.09,P=0.001),对总生存期、中位无进展生存期、无病生存期、两年生存率也有一定的改善作用。在安全性方面,联合治疗能显著降低非小细胞肺癌患者总体不良反应发生率、消化道反应发生率(RR=0.83,95%CI:0.70~0.98,P=0.03)和骨髓抑制发生率(RR=0.64,95%CI:0.53~0.77,P<0.001)。结论复方苦参注射液联合PD-1/PD-L1抑制剂治疗能提高非小细胞肺癌的临床疗效,且安全性良好。展开更多
文摘以往的研究主要集中在肿瘤细胞在免疫逃逸中的变化,而对肿瘤微环境(tumor microenvironment, TME)对免疫逃逸的影响知之甚少。肿瘤相关成纤维细胞(tumor-associated fibroblasts, TAFs)是TME的重要组成部分,具有特殊的生理生化特性,但其具体机制尚不清楚。为了研究TAF对胃癌细胞PD-L1表达的影响,通过transwell将胃癌细胞株MNK45、SGC7901与TAFs非接触共培养1、3、7 d。采用qRT-PCR和流式细胞仪检测PD-L1 mRNA和蛋白表达。然后选择95例胃癌组织,通过免疫组化检测PD-L1和TAFs的表达。结果显示,实验组PD-L1 mRNA和蛋白表达量均显著高于对照组。胃癌中PD-L1的表达与大量淋巴细胞浸润、弥漫性/混合性组织学和瘤内TAFs有关。综上所述,TAFs通过提高PD-L1的表达促进胃癌细胞株的生长。Previous studies have focused on the changes of tumour cells in immune escape, and less is known about the effect of the tumour microenvironment (TME) on immune escape. Tumour-associated fibroblasts (TAFs) cells are an important part of the TME and have special physiological and biochemical characteristics, but the specific mechanism has not been clarified. In order to investigate the effect of TAFs on the expression of PD-L1 in gastric cancer cells, gastric cancer cell lines MNK45, SGC7901 were non-contact coculturing with TAFs 1, 3 and 7 d via transwell. PD-L1 mRNA and protein expression were detected using qRT-PCR and FCM. Then, 95 cases of gastric cancer tissues were selected and PD-L1 and TAFs expressions were determined by immunohistochemical examination. The results showed that the mRNA and protein expression of PD-L1 in the experiment group were significantly higher than that in the control group. PD-L1 expression was associated with massive lymphocyte infiltration, diffuse/mixed histology and intratumoral TAFs in gastric cancers. In conclusion, TAFs promoted the growth of gastric cancer cell lines by increasing the PD-L1 expression.
文摘放疗与以免疫检查点抑制剂(如PD-1/PD-L1抑制剂)为主的免疫治疗,是实体瘤治疗的关键手段。本文聚焦放疗的免疫调节效应与二者联合应用,阐述放疗对正向免疫调节的作用机制、放疗与PD-1/PD-L1抑制剂联合时对肿瘤免疫微环境影响,远隔效应的发生等。相关临床试验显示,该联合治疗在非小细胞肺癌、肝细胞癌等多种实体瘤中展现出良好效果,但不同癌种获益有别。目前,联合治疗的最佳剂量、分割方案及时间安排策略尚存争议,需依据肿瘤类型和治疗目标进行个体化调整。本文系统梳理现有研究,为放疗与PD-1/PD-L1抑制剂联合治疗的临床实践提供全面科学依据与实用参考。Radiotherapy and immunotherapy mainly based on immune checkpoint inhibitors (such as PD-1/PD-L1 inhibitors) are key approaches for the treatment of solid tumors. This article focuses on the immunomodulatory effects of radiotherapy and their combined application. It elaborates on the mechanisms of radiotherapy’s positive immunomodulation, the impact of the combination of radiotherapy and PD-1/PD-L1 inhibitors on the tumor immune microenvironment, and the occurrence of the abscopal effect. Relevant clinical trials have demonstrated that this combined treatment has shown good efficacy in various solid tumors such as non-small cell lung cancer and hepatocellular carcinoma, yet the benefits vary among different cancer types. Currently, there are still controversies regarding the optimal dose, fractionation scheme, and timing strategy of the combined treatment, which need to be adjusted individually according to the tumor type and treatment goals. This article systematically reviews the existing research, providing a comprehensive scientific basis and practical reference for the clinical practice of the combined treatment of radiotherapy and PD-1/PD-L1 inhibitors.
文摘目的系统评价复方苦参注射液联合程序性死亡受体1(programmed death receptor 1,PD-1)/程序性死亡配体1(programmed death ligand 1,PD-L1)抑制剂治疗非小细胞肺癌的临床疗效及安全性。方法文献检索限定时间为从建库至2025年6月23日,在计算机检索PubMed、Embase、Cochrane library、知网、维普、万方和中国生物医学文献数据库关于复方苦参注射液联合PD-1/PD-L1抑制剂治疗非小细胞肺癌的随机对照试验。根据纳排标准筛选文献后,采用Cochrane偏倚风险评估工具进行质量评价,使用Revman 5.4进行统计学分析。结果共纳入6篇文献,包含患者520例。Meta分析结果显示:在临床疗效方面,相比于PD-1/PD-L1抑制剂治疗方案组,复方苦参注射液联合PD-1/PD-L1抑制剂治疗方案组能有效改善客观缓解率(RR=1.66,95%CI:1.36~2.03,P<0.001)、疾病控制率(RR=1.24,95%CI:1.08~1.42,P=0.002)和卡氏功能状态评分(MD=5.66,95%CI:2.22~9.09,P=0.001),对总生存期、中位无进展生存期、无病生存期、两年生存率也有一定的改善作用。在安全性方面,联合治疗能显著降低非小细胞肺癌患者总体不良反应发生率、消化道反应发生率(RR=0.83,95%CI:0.70~0.98,P=0.03)和骨髓抑制发生率(RR=0.64,95%CI:0.53~0.77,P<0.001)。结论复方苦参注射液联合PD-1/PD-L1抑制剂治疗能提高非小细胞肺癌的临床疗效,且安全性良好。
