肿瘤免疫原性决定了CD8+ T 细胞在免疫疗法中对TCF1的依赖。
Tumor immunogenicity dictates reliance on TCF1 in CD8+ T cells for response to immunotherapy.
发表日期：2023 Aug 17
作者：
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
来源：
CANCER CELL
摘要：
干细胞样CD8+ T细胞受T细胞因子1（TCF1）调控，被认为是免疫检查点阻断（ICB）反应所需。然而，最近的研究发现，在肿瘤环境中，依赖TCF1+CD8+ T细胞对ICB疗效可能有所不同。我们发现，在积累TOX+功能不全T细胞的免疫原性差的肿瘤中，TCF1对肿瘤特异性CD8+ T细胞的最佳激活和ICB反应是必需的，但在高免疫原性肿瘤中有效扩增临时效应细胞的T细胞激活和治疗反应中是不必要的。重要的是，通过疫苗接种或提高肿瘤上抗原呈递能力来改善T细胞激活，可以挽救在免疫原性差的肿瘤中TCF1缺失CD8+ T细胞的ICB反应缺陷。我们的研究突显了TCF1在抗肿瘤CD8+ T细胞早期阶段反应中的作用，对指导低TCF1+CD8+ T细胞和低新抗原表达肿瘤的最佳治疗干预具有重要意义。Copyright © 2023 Elsevier Inc. All rights reserved.
Stem-like CD8+ T cells are regulated by T cell factor 1 (TCF1) and are considered requisite for immune checkpoint blockade (ICB) response. However, recent findings indicate that reliance on TCF1+CD8+ T cells for ICB efficacy may differ across tumor contexts. We find that TCF1 is essential for 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 response in highly immunogenic tumors that efficiently expand transitory effectors. Importantly, improving T cell priming by vaccination or by enhancing antigen presentation on tumors rescues the defective responses of TCF1-deficient CD8+ T cells upon ICB in poorly immunogenic tumors. Our study highlights TCF1's role during the early stages of anti-tumor CD8+ T cell responses with important implications for guiding optimal therapeutic interventions in cancers with low TCF1+CD8+ T cells and low-neo-antigen expression.Copyright © 2023 Elsevier Inc. All rights reserved.