Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1+ CD8+ T cells in tumor-draining lymph nodes
In tumors, a subset of CD8+ T cells expressing the transcription factor TCF-1 drives the response to immune checkpoint blockade. We examined the mechanisms that maintain these cells in an autochthonous model of lung adenocarcinoma. Longitudinal sampling and single-cell sequencing of tumor-antigen sp...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2022
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| Online Access: | https://hdl.handle.net/1721.1/146817 |
| _version_ | 1826210560068288512 |
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| author | Schenkel, Jason M Herbst, Rebecca H Canner, David Li, Amy Hillman, Michelle Shanahan, Sean-Luc Gibbons, Grace Smith, Olivia C Kim, Jonathan Y Westcott, Peter Hwang, William L Freed-Pastor, William A Eng, George Cuoco, Michael S Rogers, Patricia Park, Jin K Burger, Megan L Rozenblatt-Rosen, Orit Cong, Le Pauken, Kristen E Regev, Aviv Jacks, Tyler |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Schenkel, Jason M Herbst, Rebecca H Canner, David Li, Amy Hillman, Michelle Shanahan, Sean-Luc Gibbons, Grace Smith, Olivia C Kim, Jonathan Y Westcott, Peter Hwang, William L Freed-Pastor, William A Eng, George Cuoco, Michael S Rogers, Patricia Park, Jin K Burger, Megan L Rozenblatt-Rosen, Orit Cong, Le Pauken, Kristen E Regev, Aviv Jacks, Tyler |
| author_sort | Schenkel, Jason M |
| collection | MIT |
| description | In tumors, a subset of CD8+ T cells expressing the transcription factor TCF-1 drives the response to immune checkpoint blockade. We examined the mechanisms that maintain these cells in an autochthonous model of lung adenocarcinoma. Longitudinal sampling and single-cell sequencing of tumor-antigen specific TCF-1+ CD8+ T cells revealed that while intratumoral TCF-1+ CD8+ T cells acquired dysfunctional features and decreased in number as tumors progressed, TCF-1+ CD8+ T cell frequency in the tumor draining LN (dLN) remained stable. Two discrete intratumoral TCF-1+ CD8+ T cell subsets developed over time-a proliferative SlamF6+ subset and a non-cycling SlamF6- subset. Blocking dLN egress decreased the frequency of intratumoral SlamF6+ TCF-1+ CD8+ T cells. Conventional type I dendritic cell (cDC1) in dLN decreased in number with tumor progression, and Flt3L+anti-CD40 treatment recovered SlamF6+ T cell frequencies and decreased tumor burden. Thus, cDC1s in tumor dLN maintain a reservoir of TCF-1+ CD8+ T cells and their decrease contributes to failed anti-tumor immunity. |
| first_indexed | 2024-09-23T14:51:53Z |
| format | Article |
| id | mit-1721.1/146817 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:51:53Z |
| publishDate | 2022 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1468172022-12-10T03:10:35Z Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1+ CD8+ T cells in tumor-draining lymph nodes Schenkel, Jason M Herbst, Rebecca H Canner, David Li, Amy Hillman, Michelle Shanahan, Sean-Luc Gibbons, Grace Smith, Olivia C Kim, Jonathan Y Westcott, Peter Hwang, William L Freed-Pastor, William A Eng, George Cuoco, Michael S Rogers, Patricia Park, Jin K Burger, Megan L Rozenblatt-Rosen, Orit Cong, Le Pauken, Kristen E Regev, Aviv Jacks, Tyler Massachusetts Institute of Technology. Department of Biology In tumors, a subset of CD8+ T cells expressing the transcription factor TCF-1 drives the response to immune checkpoint blockade. We examined the mechanisms that maintain these cells in an autochthonous model of lung adenocarcinoma. Longitudinal sampling and single-cell sequencing of tumor-antigen specific TCF-1+ CD8+ T cells revealed that while intratumoral TCF-1+ CD8+ T cells acquired dysfunctional features and decreased in number as tumors progressed, TCF-1+ CD8+ T cell frequency in the tumor draining LN (dLN) remained stable. Two discrete intratumoral TCF-1+ CD8+ T cell subsets developed over time-a proliferative SlamF6+ subset and a non-cycling SlamF6- subset. Blocking dLN egress decreased the frequency of intratumoral SlamF6+ TCF-1+ CD8+ T cells. Conventional type I dendritic cell (cDC1) in dLN decreased in number with tumor progression, and Flt3L+anti-CD40 treatment recovered SlamF6+ T cell frequencies and decreased tumor burden. Thus, cDC1s in tumor dLN maintain a reservoir of TCF-1+ CD8+ T cells and their decrease contributes to failed anti-tumor immunity. 2022-12-09T18:28:46Z 2022-12-09T18:28:46Z 2021 2022-12-09T18:15:55Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/146817 Schenkel, Jason M, Herbst, Rebecca H, Canner, David, Li, Amy, Hillman, Michelle et al. 2021. "Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1+ CD8+ T cells in tumor-draining lymph nodes." Immunity, 54 (10). en 10.1016/J.IMMUNI.2021.08.026 Immunity Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Schenkel, Jason M Herbst, Rebecca H Canner, David Li, Amy Hillman, Michelle Shanahan, Sean-Luc Gibbons, Grace Smith, Olivia C Kim, Jonathan Y Westcott, Peter Hwang, William L Freed-Pastor, William A Eng, George Cuoco, Michael S Rogers, Patricia Park, Jin K Burger, Megan L Rozenblatt-Rosen, Orit Cong, Le Pauken, Kristen E Regev, Aviv Jacks, Tyler Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1+ CD8+ T cells in tumor-draining lymph nodes |
| title | Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1+ CD8+ T cells in tumor-draining lymph nodes |
| title_full | Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1+ CD8+ T cells in tumor-draining lymph nodes |
| title_fullStr | Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1+ CD8+ T cells in tumor-draining lymph nodes |
| title_full_unstemmed | Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1+ CD8+ T cells in tumor-draining lymph nodes |
| title_short | Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1+ CD8+ T cells in tumor-draining lymph nodes |
| title_sort | conventional type i dendritic cells maintain a reservoir of proliferative tumor antigen specific tcf 1 cd8 t cells in tumor draining lymph nodes |
| url | https://hdl.handle.net/1721.1/146817 |
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