PD-1/PD-L1抑制剂治疗转移性结直肠癌研究进展

程序性细胞死亡受体1(PD-1)及其配体1(PD-L1)是参与免疫反应的关键抑制因子之一。肿瘤细胞PDL1高表达,可导致T细胞衰竭,从而实现免疫逃逸。因此,以PD-1/PD-L1抑制剂为主的免疫治疗能够用于转移性结直肠癌(mCRC)患者,并且相关的临床试验正在进行。研究发现,错配基因修复缺失(dMMR)/高度微卫星不稳定性mCRC患者PD-L1阳性表达率高,是PD-1/PD-L1抑制剂免疫疗法的优势人群,免疫治疗效果较好。而错配修复功能完整/微卫星稳定mCRC患者免疫治疗无肯定效果。PD-L1、dMMR、肿瘤突变负荷等生物标志物有助于选择免疫治疗有效的肿瘤患者,但目前这些生物标志物还难以准确地预测肿瘤免疫治疗效果。     

PD-1/PD-L1抑制剂在晚期结直肠癌中应用的研究进展

结直肠癌是世界范围内常见的恶性肿瘤,近年来其发病率不断上升,发病人群日趋年轻化.目前,手术切除仍然是结直肠癌的首选治疗方法.但结直肠癌早期症状隐匿,大多数患者在就诊时已处于晚期,错过了最佳手术时机.而针对晚期结直肠癌(mCRC)的治疗方式主要有放疗、化疗、分子靶向治疗等,但往往随着治疗日久而出现大量并发症或耐药现象.免...     

PD-1/PD-L1免疫检查点抑制剂治疗胰腺癌研究进展

肿瘤免疫治疗已成为当前肿瘤治疗领域的研究热点,其中程序性死亡受体1(PD-1)/程序性死亡受体配体1(PD-L1)通路抑制剂已在多种类型肿瘤的临床治疗中展现疗效。本文就PD-1/PD-L1抑制剂在胰腺癌治疗中的热点问题进行综述。     

PD-1/PD-L1通路在非小细胞肺癌中的研究进展

程序性死亡受体-1(PD-1)/程序性死亡配体-1(PD-L1)信号途径参与肿瘤的免疫逃逸。PD-L1蛋白在非小细胞肺癌组织中存在不同程度的表达,其表达程度与肿瘤细胞的分化程度、临床分期、淋巴转移及预后等相关联。PD-L1可能通过保持非小细胞肺癌肿瘤浸润性树突状细胞的不成熟状态,增强调节性 T 细胞功能,与浸润性淋巴细胞表面高表达的 PD-1相互作用诱导 CD8+ T 细胞凋亡等机制介导肺癌的免疫豁免。目前针对 PD-1/PD-L1途径的临床免疫治疗试验已经在非小细胞肺癌中取得一定的疗效,成为非小细胞肺癌免疫治疗的新靶向。     

PD-1/PD-L1抗体对胃癌的预后生存及不良反应的影响

目的 探讨采取程序性死亡受体-1/程序性死亡配体-1(PD-1/PD-L1)抗体治疗胃癌,对患者预后生存及不良反应的影响。方法 选取2020年1月至2021年12月在江油市第二人民医院治疗的胃癌患者122例,随机分为2组,研究组61例和对照组61例,对照组采取多西他赛治疗,研究组在对照组的基础上采取PD-1/PD-L1抗体治疗。比较两组治疗前后的血清肿瘤标记物血清糖类抗原199(CA199)、糖类抗原724(CA724)、癌胚抗原(CEA),以及无进展生存期、总生存期、不良反应、临床治疗疗效。结果 与治疗前比较,治疗后两组CA199、CA724、CEA均降低(P<0.05),且治疗后研究组CA199、CA724、CEA明显低于对照组(P<0.05)。与对照组比较,研究组的无进展生存期、总生存期明显较长(P<0.05)。两组恶心呕吐、食欲减退、疲倦分级和总发生率比较,均无统计学意义(P>0.05);与对照组比较,研究组皮肤瘙痒、皮疹、腹泻分级更低(P<0.05),研究组皮肤瘙痒、皮疹发生率、腹泻发生率明显较低(P<0.05)。与对照组比较,研究组的临床...     

PD-1/PD-L 1抗体在非小细胞肺癌治疗中的研究现状

程序性死亡因子1(programmed death-1,PD-1)存在于活化的T细胞和 B细胞表面,是一种重要的免疫共抑制分子。当 PD-1与程序性死亡配体1/2(programmed death-ligand 1/2, PD-L1/2)结合后,可以引起一系列的免疫抑制作用,并使肿瘤逃避免疫破坏。阻断 PD-1/PD-L1通路,则可能减弱其对免疫活性细胞的抑制作用,从而达到增强细胞免疫、杀灭肿瘤细胞的目的。目前大量研究证明PD-1/PD-L1抗体在非小细胞肺癌治疗中有显著的抗肿瘤活性。本文将对其研究现状加以综述。     

PD-1/PD-L1信号通路与慢性乙型肝炎

目的：程序性死亡分子-1（programmed death-1,PD-1）是近年来发现的属于B7/CD28家族的重要协同刺激分子,与其配体（programmed death -1 ligand,PD-L）结合后在调节T淋巴细胞的活化、分化及增殖功能方面起着重要作用。在慢性HBV感染不同阶段,PD-1表达水平存在差异,且与肝脏炎症程度、ALT及病毒载量等密切相关。通过不同途径阻断PD-1/PD-L1通路可以使耗竭的T淋巴细胞功能得到改善,提示可能是未来抗病毒治疗的方向之一。     

PD-1抗体/PD-L1抗体在结直肠癌治疗中的应用现状及展望

结直肠癌是第二大最常见的肿瘤死亡原因。免疫治疗逐渐成为结直肠癌手术切除等常规治疗方式以外的另一种治疗方法。目前对抗PD-1/抗PD-L1药物疗效及不良反应的报道各不相同。本文将从PD-1信号通路及其阻断剂、PD-1/PD-L1抗体在结直肠癌中的临床应用、结直肠癌患者对免疫治疗的抵抗、PD-1/PD-L1抗体治疗的不良反应、预测PD-1/PD-L1抗体治疗疗效的生物学标志物等方面进行综述。     

PD-1/PD-L通路对乙型肝炎病毒感染结局的影响

程序性死亡因子-1(programmed death 1,PD-1)是可以表达在T淋巴细胞膜表面的负向协同刺激分子受体,他与PD-1配体(programmeddeath 1 ligand,PD-L)形成通路后,可以减弱T淋巴细胞免疫反应,甚至导致T淋巴细胞功能衰竭.近来研究表明PD-I/PD-L通路的形成可以影响HBV...     

Contributions of PD-1/PD-L1 pathway to interactions of myeloid DCs with T cells in atherosclerosis

Although inflammatory cells contribute to immunopathogenesis of atherosclerosis, underlying molecular mechanisms remain largely undefined. Recently, it has been demonstrated in mouse model that Programmed death-1 (PD-1)/PD-1 ligand (PD-L) pathway plays a critical role in proatherogenic immune responses. Here we examined the expression of PD-1 and PD-L1 on peripheral blood mononuclear cells by flow cytometry in 76 patients with coronary artery disease (CAD), and 25 healthy volunteers. The expression of PD-1 and PD-L1 is significantly down-regulated on T cells and myeloid dendritic cells (mDCs) in CAD patients than in healthy individuals, respectively. More importantly, we found that decreased PD-L1 expression on mDCs is related with the increased T cell immune responses in CAD patients. In addition, stimulation of PD-L1 expression in vitro could attenuate the stimulatory ability on allogeneic T cell proliferation and its cytokine production, including IFN-γ and IL-2, and also influence the production of IL-10 and IL-12 by mDCs. Taken together, we can draw a conclusion that PD-1/PD-L1 pathway plays a key role in the regulation of proatherogenic T cell immunity by intervening antigen presenting cell (APC)-dependent T cell activation, which associates with pro-inflammatory or anti-inflammatory cytokine production, and further studies need gain insight into that this pathway represents a strategy of immunotherapy for atherosclerosis.     

MMR与PD-L1在Ⅱ期术后结直肠癌中的差异性表达

目的探讨错配修复基因（MMR）和细胞程序性死亡配体1（PD-L1）在Ⅱ期结直肠癌（CRC）组织中的一致性及差异性。 方法选取2016年1月到2017年10月接受手术治疗的Ⅱ期CRC患者50例,免疫组化法检测术后病理组织标本中4种MMR蛋白：MutL同源蛋白1（MLH1）、Muts同源蛋白2（MSH2）、Muts同源蛋白6（MSH6）、减数分裂后分离蛋白2（PMS2）和PD-L1的表达,并分析二者的相关性。 结果结直肠癌组织中MMR缺失（dMMR）率和PD-L1的阳性率分别为32%（16/50）和38%（19/50）,dMMR和PD-L1双阳性的患者为20%（10/50）;dMMR患者中PD-L1的阳性率高于错配修复功能完整患者,62.5%（10/16）vs 26.5%（9/34）,差异具有统计学意义（χ²=5.995,P=0.027）,PD-L1的表达与MLH1和MSH2表达缺失有关（P=0.024和0.049）;PD-L1阳性患者（n=19）中dMMR与错配修复功能完整的发生率差异无统计学意义,52.6% vs 47.4%。 结论PD-L1蛋白与dMMR存在差异性表达,在使用靶向药物治疗前,应综合考虑两种生物标志物的表达情况更精准地筛选患者。     

Dendritic cell-based cancer immunotherapy for colorectal cancer

Colorectal cancer(CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients.     

PD-1/PD-L1信号通路在乙型病毒性肝炎免疫调节作用的研究进展

程序性死亡分子1(programmed death-1,PD-1)是由pdcdl基因编码的一个抑制性共刺激分子,在维持外周耐受中起着关键性的作用,并在慢性病毒感染、肿瘤免疫及自身免疫性疫病的发生过程中发挥重要的生物学作用,受到广泛的关注.本文主要综述PD-1/PD-L1信号通路在乙型病毒性肝炎免疫调节作用的研究进展.     

Expression pattern of PD-1/PD-L1 in primary liver cancer with clinical correlation

Immunotherapy, including ICIs, has emerged as an invaluable treatment option for advanced PLC. Nevertheless, the expression patterns of PD-L1 and PD-1 in PLC remain incompletely understood. In this study, the expression pattern and clinical correlation of PD-L1 and PD-1 were analysed in 5245 PLC patients. The positivity rates of PD-L1 and PD-1 were very low in the patient PLCs, but the positivity rates of PD-L1 and PD-1 were higher in the ICC and cHCC-ICC than in HCC. The expression of PD-L1 and PD-1 correlated with the malignant phenotypes and clinicopathological characteristics of PLC. Interestingly, PD-1 positivity might serve as an independent prognostic factor. Based on a systematic analysis of a large amount of PLC tissues, we proposed a novel classification of PD-1/PD-L1 expression in HCC and ICC. In light of this stratification, we observed a close correlation between PD-L1 levels and PD-1 expression in HCC and ICC.     

慢性乙型肝炎病毒感染者肝组织中程序性死亡分子-1及其配体的表达

目的 通过比较慢性HBV感染免疫耐受期和免疫清除期的患者肝组织中程序性死亡分子-1及其配体的表达情况,探讨其与机体免疫功能状态的关系.方法 收集肝组织活体检查标本并分为免疫清除期组25例、免疫耐受期组19例,用免疫组织化学方法检测标本汇管区中T淋巴细胞程序性死亡分子-1及其配体的表达情况,通过半定量评分系统计算其占CD3阳性细胞的百分数,用t检验比较两组病例间程序性死亡分子-1及其配体表达的差异.结果 免疫耐受期组肝组织汇管区T淋巴细胞中程序性死亡分子-1所占CD3阳性细胞比率为63.79%±6.94%,高于免疫清除期的54.36%±10.08%,两组比较,t=3.492,P<0.01,差异有统计学意义;程序性死亡分子配体-1于T淋巴细胞中的表达在免疫耐受期组(66.47%±8.40%)中高于免疫清除期组(52.64%±6.20%),两组比较,t=6.288,P<0.01,差异有统计学意义.程序性死亡分子配体-1在枯否细胞中的表达强度及范围在两组间差异无统计学意义(P>0.05).结论 慢性HBV感染者肝组织中的程序性死亡分子-1及其配体表达水平的差异反映了免疫耐受期和免疫清除期的不同免疫功能状态.

Abstract：

Objective To detect and compare the PD- 1/PD-L1 (programmed death 1/programmed death 1 ligand) expressions in the liver tissues of chronic HBV infection patients in immune tolerant phase and those in immune clearance phase. Methods Liver biopsy samples were divided into two groups: 25 samples from patients in immune clearance phase and 19 samples from patients in immune tolerant phase.PD-1/PD-L1 expressions on T lymphocytes in these liver biopsy specimens were detected by immunobis tochemistry method. Percentage of PD-1/PD-L1 positive cells among CD3 positive cells was calculated by semi-quantitative evaluation. Differences between the two groups were statistically analyzed. Results PD1/PD-L1 expressions were significantly higher in the patients in immune tolerant phase as compared to that in immune active phase (P < 0.05). No statistical difference found between the two groups for PD-L1 expression in Kupffer cells (P > 0.05). Conclusion PD-1/PD-L1 expression level can reflect the immune functions of chronic hepatitis B patients.