小柯机器人

中山大学邓艳红研究组发现，PD-1阻断在错配修复缺陷结结直肠癌(CRCs)中免疫和基质细胞室的重塑。相关论文于2023年5月11日发表在《癌细胞》杂志上。

他们利用单细胞RNA测序(scRNA-seq)研究了19例接受新辅助PD-1阻断治疗的d-MMR/MSI-H CRC患者的免疫和基质细胞动力学。他们发现，在病理完全反应(pCR)肿瘤中，治疗后CD8+ Trm -有丝分裂细胞、CD4+ Tregs、促炎IL1B + Mono和CCL2+成纤维细胞的比例一致下降，而CD8+ Tem、CD4+ Th、CD20+ B和HLA-DRA+内皮细胞的比例增加。肿瘤微环境中的促炎特征通过调节CD8+ T细胞和其他反应相关的免疫细胞群介导残留肿瘤的持续存在。

他们的研究为免疫检查点抑制剂(ICI)成功治疗的机制，和提高治疗效果的潜在靶点提供了宝贵的资源和生物学见解。

研究人员表示，ICI治疗可诱导错配修复缺陷和微卫星不稳定性高(d-MMR/MSI-H) CRC的完全缓解。然而，pCR对免疫治疗的潜在机制尚未完全了解。

附：英文原文

Title: Remodeling of the immune and stromal cell compartment by PD-1 blockade in mismatch repair-deficient colorectal cancer

Author: Jianxia Li, Cheng Wu, Huabin Hu, Ge Qin, Xueqian Wu, Fan Bai, Jianwei Zhang, Yue Cai, Yan Huang, Chao Wang, Jiaqi Yang, Yizhao Luan, Zehang Jiang, Jiayu Ling, Zehua Wu, Yaoxu Chen, Zhi Xie, Yanhong Deng

Issue&Volume: 2023-05-11

Abstract: Immune checkpoint inhibitor (ICI) therapy can induce complete responses in mismatchrepair-deficient and microsatellite instability-high (d-MMR/MSI-H) colorectal cancers(CRCs). However, the underlying mechanism for pathological complete response (pCR)to immunotherapy has not been completely understood. We utilize single-cell RNA sequencing(scRNA-seq) to investigate the dynamics of immune and stromal cells in 19 patientswith d-MMR/MSI-H CRC who received neoadjuvant PD-1 blockade. We found that in tumorswith pCR, there is a concerted decrease in CD8+ Trm-mitotic, CD4+ Tregs, proinflammatory IL1B+ Mono and CCL2+ Fibroblast following treatment, while the proportions of CD8+ Tem, CD4+ Th, CD20+ B, and HLA-DRA+ Endothelial cells increase. Proinflammatory features in the tumor microenvironmentmediate the persistence of residual tumors by modulating CD8+ T cells and other response-associated immune cell populations. Our study providesvaluable resources and biological insights into the mechanism of successful ICI therapyand potential targets for improving treatment efficacy.

DOI: 10.1016/j.ccell.2023.04.011

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00137-X

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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