Cui Guanglin
Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Faculty of Health Science, Nord University, Bodø, Norway.
Front Oncol. 2021 Mar 5;11:573547. doi: 10.3389/fonc.2021.573547. eCollection 2021.
Current clinical studies showed distinct therapeutic outcomes, in which CRC patients with mismatch repair-deficient (dMMR)/microsatellite instability high (MSI-H) seem to be relatively more "sensitive" in response to anti-programmed death-1 receptor (PD-1)/programmed death-1 receptor ligand 1 (PD-L1) therapy than those with mismatch repair-proficient (pMMR)/microsatellite instability-low (MSI-L). The mechanisms by which the same PD-1/PD-L1 blockades lead to two distinct therapeutic responses in CRC patients with different MSI statuses remain poorly understood and become a topic of great interest in both basic research and clinical practice. In this review of the potential mechanisms for the distinct response to PD-1/PD-L1 blockades between dMMR/MSI-H CRCs and pMMR/MSI-L CRCs, relevant references were electronically searched and collected from databases PubMed, MEDLINE, and Google scholar. Sixty-eight articles with full text and 10 articles by reference-cross search were included for final analysis after eligibility selection according to the guidelines of PRISMA. Analysis revealed that multiple factors tumor mutation burden, immune cell densities and types in the tumor microenvironment, expression levels of PD-1/PD-L1 and cytokines are potential determinants of such distinct response to PD-1/PD-L1 blockades in CRC patients with different MSI statuses which might help clinicians to select candidates for anti-PD-1/PD-L1 therapy and improve therapeutic response in patients with CRC.
目前的临床研究显示出截然不同的治疗结果，其中错配修复缺陷（dMMR）/微卫星高度不稳定（MSI-H）的结直肠癌患者似乎比错配修复功能正常（pMMR）/微卫星低度不稳定（MSI-L）的患者对抗程序性死亡1受体（PD-1）/程序性死亡1受体配体1（PD-L1）治疗的反应相对更“敏感”。对于具有不同微卫星状态的结直肠癌患者，相同的PD-1/PD-L1阻断剂为何会导致两种截然不同的治疗反应，目前仍知之甚少，这已成为基础研究和临床实践中备受关注的话题。在这篇关于dMMR/MSI-H结直肠癌和pMMR/MSI-L结直肠癌对PD-1/PD-L1阻断剂产生不同反应的潜在机制的综述中，通过电子检索从PubMed、MEDLINE和谷歌学术数据库中搜索并收集了相关参考文献。根据PRISMA指南进行合格性筛选后，纳入68篇全文文章和10篇通过参考文献交叉检索得到的文章进行最终分析。分析表明，多种因素——肿瘤突变负荷、肿瘤微环境中的免疫细胞密度和类型、PD-1/PD-L1和细胞因子的表达水平——是具有不同微卫星状态的结直肠癌患者对PD-1/PD-L1阻断剂产生这种不同反应的潜在决定因素，这可能有助于临床医生选择抗PD-1/PD-L1治疗的候选患者，并提高结直肠癌患者的治疗反应。
