美国哈佛医学院和布莱根妇女医院Ana C. Anderson课题组探明，肿瘤免疫原性决定了CD8+ T细胞对免疫治疗的应答依赖于T细胞因子1 (TCF1)。该研究于2023年8月24日发表于国际一流学术期刊《癌细胞》杂志上。

他们发现TCF1对于肿瘤抗原特异性CD8+ T细胞的最佳启动，和在积累TOX+功能失调T细胞的低免疫原性肿瘤中的免疫检查点阻断(ICB)反应，是必不可少的，但对于有效扩展短暂效应物的高免疫原性肿瘤的T细胞启动和治疗反应是可有可无的。重要的是，通过接种疫苗或增强肿瘤抗原呈递来改善T细胞的启动，可以在免疫原性差的肿瘤中挽救tcf1缺陷CD8+ T细胞对ICB的缺陷反应。

他们的研究强调了TCF1在抗肿瘤CD8+ T细胞应答的早期阶段的作用，这对于指导低TCF1+CD8+ T细胞和低新抗原表达的癌症的最佳治疗干预具有重要意义。

据悉，干细胞样CD8+ T细胞受TCF1调控，被认为是ICB应答所必需的。

附：英文原文

Title: Tumor immunogenicity dictates reliance on TCF1 in CD8+ T cells for response to immunotherapy

Author: Giulia Escobar, Katherine Tooley, Joan Pagès Oliveras, Linglin Huang, Hanning Cheng, Michelle L. Bookstaver, Camilla Edwards, Eugene Froimchuk, Chang Xue, Davide Mangani, Rajesh K. Krishnan, Natanael Hazel, Carola Rutigliani, Christopher M. Jewell, Luca Biasco, Ana C. Anderson

Issue&Volume: 2023-08-24

Abstract: Stem-like CD8+ T cells are regulated by T cell factor 1 (TCF1) and are considered requisite forimmune checkpoint blockade (ICB) response. However, recent findings indicate thatreliance on TCF1+CD8+ T cells for ICB efficacy may differ across tumor contexts. We find that TCF1 is essentialfor optimal priming of tumor antigen-specific CD8+ T cells and ICB response in poorly immunogenic tumors that accumulate TOX+ dysfunctional T cells, but is dispensable for T cell priming and therapy responsein highly immunogenic tumors that efficiently expand transitory effectors. Importantly,improving T cell priming by vaccination or by enhancing antigen presentation on tumorsrescues the defective responses of TCF1-deficient CD8+ T cells upon ICB in poorly immunogenic tumors. Our study highlights TCF1’s role duringthe early stages of anti-tumor CD8+ T cell responses with important implications for guiding optimal therapeutic interventionsin cancers with low TCF1+CD8+ T cells and low-neo-antigen expression.

DOI: 10.1016/j.ccell.2023.08.001

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00273-8