Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors
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 expan...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Elsevier BV
2022
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| Online Access: | https://hdl.handle.net/1721.1/146816 |
| _version_ | 1826208521772859392 |
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| author | Burger, Megan L Cruz, Amanda M Crossland, Grace E Gaglia, Giorgio Ritch, Cecily C Blatt, Sarah E Bhutkar, Arjun Canner, David Kienka, Tamina Tavana, Sara Z Barandiaran, Alexia L Garmilla, Andrea Schenkel, Jason M Hillman, Michelle de los Rios Kobara, Izumi Li, Amy Jaeger, Alex M Hwang, William L Westcott, Peter MK Manos, Michael P Holovatska, Marta M Hodi, F Stephen Regev, Aviv Santagata, Sandro Jacks, Tyler |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Burger, Megan L Cruz, Amanda M Crossland, Grace E Gaglia, Giorgio Ritch, Cecily C Blatt, Sarah E Bhutkar, Arjun Canner, David Kienka, Tamina Tavana, Sara Z Barandiaran, Alexia L Garmilla, Andrea Schenkel, Jason M Hillman, Michelle de los Rios Kobara, Izumi Li, Amy Jaeger, Alex M Hwang, William L Westcott, Peter MK Manos, Michael P Holovatska, Marta M Hodi, F Stephen Regev, Aviv Santagata, Sandro Jacks, Tyler |
| author_sort | Burger, Megan L |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:06:57Z |
| format | Article |
| id | mit-1721.1/146816 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:06:57Z |
| publishDate | 2022 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1468162022-12-10T03:16:32Z Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors Burger, Megan L Cruz, Amanda M Crossland, Grace E Gaglia, Giorgio Ritch, Cecily C Blatt, Sarah E Bhutkar, Arjun Canner, David Kienka, Tamina Tavana, Sara Z Barandiaran, Alexia L Garmilla, Andrea Schenkel, Jason M Hillman, Michelle de los Rios Kobara, Izumi Li, Amy Jaeger, Alex M Hwang, William L Westcott, Peter MK Manos, Michael P Holovatska, Marta M Hodi, F Stephen Regev, Aviv Santagata, Sandro Jacks, Tyler Massachusetts Institute of Technology. Department of Biology 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. 2022-12-09T18:25:19Z 2022-12-09T18:25:19Z 2021 2022-12-09T18:06:44Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/146816 Burger, Megan L, Cruz, Amanda M, Crossland, Grace E, Gaglia, Giorgio, Ritch, Cecily C et al. 2021. "Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors." Cell, 184 (19). en 10.1016/J.CELL.2021.08.020 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Burger, Megan L Cruz, Amanda M Crossland, Grace E Gaglia, Giorgio Ritch, Cecily C Blatt, Sarah E Bhutkar, Arjun Canner, David Kienka, Tamina Tavana, Sara Z Barandiaran, Alexia L Garmilla, Andrea Schenkel, Jason M Hillman, Michelle de los Rios Kobara, Izumi Li, Amy Jaeger, Alex M Hwang, William L Westcott, Peter MK Manos, Michael P Holovatska, Marta M Hodi, F Stephen Regev, Aviv Santagata, Sandro Jacks, Tyler Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors |
| title | Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors |
| title_full | Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors |
| title_fullStr | Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors |
| title_full_unstemmed | Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors |
| title_short | Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors |
| title_sort | antigen dominance hierarchies shape tcf1 progenitor cd8 t cell phenotypes in tumors |
| url | https://hdl.handle.net/1721.1/146816 |
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