美国麻省理工学院Tyler Jacks团队发现抗原优势等级塑造肿瘤中 TCF1+ 祖细胞 CD8 T 细胞表型。2021年9月16日出版的《细胞》杂志发表了这项成果。
在小鼠肺腺癌中，他们发现在肿瘤中建立了免疫优势，其中 CD8 T 细胞扩增主要由最稳定地结合 MHC 的抗原驱动。对亚优势抗原有反应的 T 细胞富集了与免疫检查点阻断 (ICB) 治疗反应相关的 TCF1+ 祖细胞表型。然而，由于以 CCR6 和 Tc17 分化为标志的功能失调的 TCF1+ 细胞亚群，亚优势 T 细胞反应并没有优先受益于 ICB。
对人类样本和测序数据集的分析表明，CCR6+ TCF1+ 细胞存在于人类癌症中，并且与 ICB 反应无关。疫苗接种消除了 CCR6+ TCF1+ 细胞并显著改善了亚显性反应，突出了一种以最佳方式进行针对肿瘤的并发新抗原反应的策略。
据悉，针对不同肿瘤新抗原的 CD8 T 细胞反应同时发生，但对反应之间的相互作用及其对 T 细胞功能和肿瘤控制的影响知之甚少。
附：英文原文
Title: Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors
Author: Megan L. Burger, Amanda M. Cruz, Grace E. Crossland, Giorgio Gaglia, Cecily C. Ritch, Sarah E. Blatt, Arjun Bhutkar, David Canner, Tamina Kienka, Sara Z. Tavana, Alexia L. Barandiaran, Andrea Garmilla, Jason M. Schenkel, Michelle Hillman, Izumi de los Rios Kobara, Amy Li, Alex M. Jaeger, William L. Hwang, Peter M.K. Westcott, Michael P. Manos, Marta M. Holovatska, F. Stephen Hodi, Aviv Regev, Sandro Santagata, Tyler Jacks
Issue&Volume: 2021/09/16
Abstract: CD8 T cell responses against different tumor neoantigens occur simultaneously, yetlittle is known about the interplay between responses and its impact on T cell functionand tumor control. In mouse lung adenocarcinoma, we found that immunodominance isestablished in tumors, wherein CD8 T cell expansion is predominantly driven by theantigen that most stably binds MHC. T cells responding to subdominant antigens wereenriched for a TCF1+ progenitor phenotype correlated with response to immune checkpoint blockade (ICB)therapy. However, the subdominant T cell response did not preferentially benefit fromICB due to a dysfunctional subset of TCF1+ cells marked by CCR6 and Tc17 differentiation. Analysis of human samples and sequencingdatasets revealed that CCR6+ TCF1+ cells exist across human cancers and are not correlated with ICB response. Vaccinationeliminated CCR6+ TCF1+ cells and dramatically improved the subdominant response, highlighting a strategyto optimally engage concurrent neoantigen responses against tumors.
DOI: 10.1016/j.cell.2021.08.020
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00994-6