错配修复缺陷的晚期结直肠癌患者丧失生存优势，可能是由于 CD8+T 细胞预后价值的改变引起的。
Loss of survival advantage for deficient mismatch repair in patients with advanced colorectal cancer may be caused by changes in prognostic value of CD8+T cell.
机构信息
Department of General Surgery, Peking University Third Hospital, Beijing, China.
Department of Pathology, School of Basic Medical Sciences, Third Hospital, Peking University Health Science Center, Beijing, China.
出版信息
World J Surg Oncol. 2020 Aug 7;18(1):196. doi: 10.1186/s12957-020-01970-0.
BACKGROUND
Patients with stage II deficient mismatch repair (dMMR) show a better prognosis than patients with colorectal cancer (CRC) with proficient mismatch repair (pMMR). However, this beneficial effect is decreased in advanced stages of the disease. This study was conducted to investigate the prognostic value of dMMR in different stage and alterations in the tumor microenvironment.
METHODS
This was a matched retrospective cohort study. Thirty-two patients with stage III&IV dMMR matched with 32 patients with stage I&II dMMR and 64 patients with pMMR were evaluated. Immunohistochemistry analysis was performed for the 64 patients with dMMR to explore the expression and prognostic effect of CD3, CD4, CD8, and PD-L1.
RESULTS
Patients with stage III-IV dMMR showed no advantage in overall survival (OS) and disease-free survival (DFS) compared to patients with pMMR (P = 0.244, P = 0.667). No expression differences in CD3, CD4, CD8, and PD-L1 at the center of the tumor (CT) or invasive margin (IM) were found between patients with stage I&II and stage III&IV dMMR. High CD3 expression at the CT and high CD3 an CD4 expression at the IM improved both OS and DFS. High CD8 expression showed opposite prognostic value in patients with stage I&II and III&IV dMMR. A similar tendency was observed for PD-L1 expression.
CONCLUSION
Patients with stage III-IV dMMR showed no prognostic advantage over patients with pMMR. Expression of CD3, CD4, CD8, and PD-L1 was similar between stage I&II and III&IV dMMR CRC. High CD3 expression at the CT and high CD3 and CD4 expression at the IM can significantly improve patient prognosis. The opposite prognostic tendency of CD8 and PD-L1 for patients with stage I&II and III&IV dMMR may be relevant to CD8+T cell exhaustion and functional changes at inhibitory immune checkpoints.
背景
与具有 proficient mismatch repair（pMMR）的结直肠癌（CRC）患者相比，Ⅱ期缺陷性 mismatch repair（dMMR）患者预后更好。然而，这种有益的效果在疾病的晚期阶段会降低。本研究旨在探讨不同分期 dMMR 及肿瘤微环境改变的预后价值。
方法
这是一项匹配的回顾性队列研究。评估了 32 例 III&IV 期 dMMR 患者与 32 例 I&II 期 dMMR 患者和 64 例 pMMR 患者相匹配。对 64 例 dMMR 患者进行免疫组织化学分析，以探讨 CD3、CD4、CD8 和 PD-L1 的表达及其预后作用。
结果
与 pMMR 患者相比，III&IV 期 dMMR 患者的总生存期（OS）和无病生存期（DFS）无优势（P = 0.244，P = 0.667）。I&II 期和 III&IV 期 dMMR 患者肿瘤中心（CT）和浸润边缘（IM）的 CD3、CD4、CD8 和 PD-L1 表达无差异。CT 处高 CD3 表达和 IM 处高 CD3 和 CD4 表达可改善 OS 和 DFS。CD8 表达高在 I&II 期和 III&IV 期 dMMR 患者中具有相反的预后价值。PD-L1 表达也存在类似的趋势。
结论
与 pMMR 患者相比，III&IV 期 dMMR 患者无预后优势。I&II 期和 III&IV 期 dMMR CRC 患者的 CD3、CD4、CD8 和 PD-L1 表达相似。CT 处高 CD3 表达和 IM 处高 CD3 和 CD4 表达可显著改善患者预后。I&II 期和 III&IV 期 dMMR 患者中 CD8 和 PD-L1 的相反预后趋势可能与 CD8+T 细胞耗竭和抑制性免疫检查点的功能变化有关。
Zotero 插件