小柯机器人

美国达纳-法伯癌症研究所Kai W. Wucherpfennig研究组与合作者取得一项新突破。他们发现了肿瘤免疫治疗诱导结肠炎症的分子途径。2020年6月29日，《细胞》杂志发表了这一成果。

他们报告了对结肠炎中免疫细胞群的综合单细胞分析，这是检验点封闭的常见而严重的副作用。他们观察到具有高度细胞毒性和增殖状态的CD8 T细胞的惊人堆积，并且没有调节性T细胞耗竭的证据。

T细胞受体（TCR）序列分析表明，与结肠炎相关的CD8 T细胞有很大一部分起源于组织定植群体，这解释了治疗开始后结肠炎症状通常较早发作的原因。他们的分析还确定了细胞因子、趋化因子和表面受体，它们可作为结肠炎和检查点封闭潜在的其他炎症副作用的治疗靶标。

据了解，用对PD-1和CTLA-4抑制受体具有特异性的抗体对检查点进行封闭，可在多种人类癌症中诱导持久性应答。然而，导致严重的炎症副作用的免疫机制仍然知之甚少。

附：英文原文

Title: Molecular Pathways of Colon Inflammation Induced by Cancer Immunotherapy

Author: Adrienne M. Luoma, Shengbao Suo, Hannah L. Williams, Tatyana Sharova, Keri Sullivan, Michael Manos, Peter Bowling, F. Stephen Hodi, Osama Rahma, Ryan J. Sullivan, Genevieve M. Boland, Jonathan A. Nowak, Stephanie K. Dougan, Michael Dougan, Guo-Cheng Yuan, Kai W. Wucherpfennig

Issue&Volume: 2020-06-29

Abstract: Checkpoint blockade with antibodies specific for the PD-1 and CTLA-4 inhibitory receptors can induce durable responses in a wide range of human cancers. However, the immunological mechanisms responsible for severe inflammatory side effects remain poorly understood. Here we report a comprehensive single-cell analysis of immune cell populations in colitis, a common and severe side effect of checkpoint blockade. We observed a striking accumulation of CD8 T cells with highly cytotoxic and proliferative states and no evidence of regulatory T cell depletion. T cell receptor (TCR) sequence analysis demonstrated that a substantial fraction of colitis-associated CD8 T cells originated from tissue-resident populations, explaining the frequently early onset of colitis symptoms following treatment initiation. Our analysis also identified cytokines, chemokines, and surface receptors that could serve as therapeutic targets for colitis and potentially other inflammatory side effects of checkpoint blockade.

DOI: 10.1016/j.cell.2020.06.001

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30688-7