Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1(+) CD8(+) T cells in the tumor draining lymph nodes
| Autor: | William L. Hwang, Megan L. Burger, Orit Rozenblatt-Rosen, Le Cong, Michael S. Cuoco, Tyler Jacks, Jonathan Y. Kim, David Canner, George Eng, Amy Li, Sean-Luc Shanahan, Peter M. K. Westcott, Olivia Smith, Patricia Rogers, Rebecca H. Herbst, Kristen E. Pauken, Grace Gibbons, Aviv Regev, Jason M. Schenkel, Jin K. Park, Michelle Hillman, William A. Freed-Pastor |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Lung Neoplasms
Immunology Adenocarcinoma of Lung Dendritic cell Dendritic Cells Biology CD8-Positive T-Lymphocytes medicine.disease Tumor antigen Immune checkpoint Article Mice Infectious Diseases Tumor progression T-Lymphocyte Subsets medicine Cancer research T Cell Transcription Factor 1 Immunology and Allergy Adenocarcinoma Cytotoxic T cell Animals Lymph Lymph Nodes CD8 |
| Zdroj: | Immunity |
| Popis: | 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 whereas 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. |
| Databáze: | OpenAIRE |
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