Antigen Dominance Hierarchies Shape TCF1+ Progenitor CD8 T Cell Phenotypes in Tumors
| Autor: | Jason M. Schenkel, Sara Z. Tavana, Michelle Hillman, Peter M. K. Westcott, Megan L. Burger, Sarah E. Blatt, Tyler Jacks, David Canner, Marta M. Holovatska, Michael Manos, Giorgio Gaglia, Izumi de los Rios Kobara, Aviv Regev, Alex M. Jaeger, Arjun Bhutkar, Sandro Santagata, William L. Hwang, F. Stephen Hodi, Cecily C. Ritch, Amanda M. Cruz, Tamina Kienka, Andrea Garmilla, Alexia L. Barandiaran, Amy Li, Grace E. Crossland |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Receptors
CCR6 Subdominant Lung Neoplasms Programmed Cell Death 1 Receptor Receptors Antigen T-Cell Adenocarcinoma of Lung Immunodominance Biology CD8-Positive T-Lymphocytes Major histocompatibility complex General Biochemistry Genetics and Molecular Biology Article Epitopes Mice Antigen Antigens Neoplasm Cytotoxic T cell Animals Humans CTLA-4 Antigen Amino Acid Sequence Hepatocyte Nuclear Factor 1-alpha RNA-Seq Immune Checkpoint Inhibitors Progenitor Stem Cells Vaccination Immune checkpoint Phenotype biology.protein Cancer research Female Single-Cell Analysis Peptides CD8 |
| Zdroj: | Cell |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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