| Literature DB >> 34534464 |
Megan L Burger1, Amanda M Cruz2, Grace E Crossland1, Giorgio Gaglia3, Cecily C Ritch3, Sarah E Blatt1, Arjun Bhutkar1, David Canner2, Tamina Kienka1, Sara Z Tavana1, Alexia L Barandiaran1, Andrea Garmilla1, Jason M Schenkel4, Michelle Hillman1, Izumi de Los Rios Kobara1, Amy Li2, Alex M Jaeger1, William L Hwang5, Peter M K Westcott1, Michael P Manos6, Marta M Holovatska6, F Stephen Hodi7, Aviv Regev8, Sandro Santagata9, Tyler Jacks10.
Abstract
CD8 T cell responses against different tumor neoantigens occur simultaneously, yet little is known about the interplay between responses and its impact on T cell function and tumor control. In mouse lung adenocarcinoma, we found that immunodominance is established in tumors, wherein CD8 T cell expansion is predominantly driven by the antigen that most stably binds MHC. T cells responding to subdominant antigens were enriched for a TCF1+ progenitor phenotype correlated with response to immune checkpoint blockade (ICB) therapy. However, the subdominant T cell response did not preferentially benefit from ICB due to a dysfunctional subset of TCF1+ cells marked by CCR6 and Tc17 differentiation. Analysis of human samples and sequencing datasets revealed that CCR6+ TCF1+ cells exist across human cancers and are not correlated with ICB response. Vaccination eliminated CCR6+ TCF1+ cells and dramatically improved the subdominant response, highlighting a strategy to optimally engage concurrent neoantigen responses against tumors.Entities:
Keywords: CCR6; CD8 T cell; TCF1; Tc17; checkpoint blockade; immunodominance; lung cancer; neoantigen; vaccine
Mesh：
Substances：
Year: 2021 PMID： 34534464 PMCID： PMC8522630 DOI： 10.1016/j.cell.2021.08.020
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 66.850