Tumor resident memory CD8 T cells and concomitant tumor immunity develop independently of CD4 help
Abstract Tissue resident memory (Trm) CD8 T cells infiltrating tumors represent an enriched population of tumor antigen-specific T cells, and their presence is associated with improved outcomes in patients. Using genetically engineered mouse pancreatic tumor models we demonstrate that tumor implanta...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-33508-1 |
| _version_ | 1797841078815031296 |
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| author | Terry R. Medler Gwen Kramer Shelly Bambina Andrew J. Gunderson Alejandro Alice Tiffany Blair Lauren Zebertavage Thomas Duhen Rebekka Duhen Kristina Young Marka R. Crittenden Michael J. Gough |
| author_facet | Terry R. Medler Gwen Kramer Shelly Bambina Andrew J. Gunderson Alejandro Alice Tiffany Blair Lauren Zebertavage Thomas Duhen Rebekka Duhen Kristina Young Marka R. Crittenden Michael J. Gough |
| author_sort | Terry R. Medler |
| collection | DOAJ |
| description | Abstract Tissue resident memory (Trm) CD8 T cells infiltrating tumors represent an enriched population of tumor antigen-specific T cells, and their presence is associated with improved outcomes in patients. Using genetically engineered mouse pancreatic tumor models we demonstrate that tumor implantation generates a Trm niche that is dependent on direct antigen presentation by cancer cells. However, we observe that initial CCR7-mediated localization of CD8 T cells to tumor draining lymph nodes is required to subsequently generate CD103+ CD8 T cells in tumors. We observe that the formation of CD103+ CD8 T cells in tumors is dependent on CD40L but independent of CD4 T cells, and using mixed chimeras we show that CD8 T cells can provide their own CD40L to permit CD103+ CD8 T cell differentiation. Finally, we show that CD40L is required to provide systemic protection against secondary tumors. These data suggest that CD103+ CD8 T cell formation in tumors can occur independent of the two-factor authentication provided by CD4 T cells and highlight CD103+ CD8 T cells as a distinct differentiation decision from CD4-dependent central memory. |
| first_indexed | 2024-04-09T16:25:13Z |
| format | Article |
| id | doaj.art-71fc1c1f57f6476d9ed4a952100a3793 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T16:25:13Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-71fc1c1f57f6476d9ed4a952100a37932023-04-23T11:15:46ZengNature PortfolioScientific Reports2045-23222023-04-0113111710.1038/s41598-023-33508-1Tumor resident memory CD8 T cells and concomitant tumor immunity develop independently of CD4 helpTerry R. Medler0Gwen Kramer1Shelly Bambina2Andrew J. Gunderson3Alejandro Alice4Tiffany Blair5Lauren Zebertavage6Thomas Duhen7Rebekka Duhen8Kristina Young9Marka R. Crittenden10Michael J. Gough11Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical CenterEarle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical CenterEarle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical CenterEarle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical CenterEarle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical CenterEarle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical CenterEarle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical CenterEarle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical CenterEarle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical CenterEarle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical CenterEarle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical CenterEarle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical CenterAbstract Tissue resident memory (Trm) CD8 T cells infiltrating tumors represent an enriched population of tumor antigen-specific T cells, and their presence is associated with improved outcomes in patients. Using genetically engineered mouse pancreatic tumor models we demonstrate that tumor implantation generates a Trm niche that is dependent on direct antigen presentation by cancer cells. However, we observe that initial CCR7-mediated localization of CD8 T cells to tumor draining lymph nodes is required to subsequently generate CD103+ CD8 T cells in tumors. We observe that the formation of CD103+ CD8 T cells in tumors is dependent on CD40L but independent of CD4 T cells, and using mixed chimeras we show that CD8 T cells can provide their own CD40L to permit CD103+ CD8 T cell differentiation. Finally, we show that CD40L is required to provide systemic protection against secondary tumors. These data suggest that CD103+ CD8 T cell formation in tumors can occur independent of the two-factor authentication provided by CD4 T cells and highlight CD103+ CD8 T cells as a distinct differentiation decision from CD4-dependent central memory.https://doi.org/10.1038/s41598-023-33508-1 |
| spellingShingle | Terry R. Medler Gwen Kramer Shelly Bambina Andrew J. Gunderson Alejandro Alice Tiffany Blair Lauren Zebertavage Thomas Duhen Rebekka Duhen Kristina Young Marka R. Crittenden Michael J. Gough Tumor resident memory CD8 T cells and concomitant tumor immunity develop independently of CD4 help Scientific Reports |
| title | Tumor resident memory CD8 T cells and concomitant tumor immunity develop independently of CD4 help |
| title_full | Tumor resident memory CD8 T cells and concomitant tumor immunity develop independently of CD4 help |
| title_fullStr | Tumor resident memory CD8 T cells and concomitant tumor immunity develop independently of CD4 help |
| title_full_unstemmed | Tumor resident memory CD8 T cells and concomitant tumor immunity develop independently of CD4 help |
| title_short | Tumor resident memory CD8 T cells and concomitant tumor immunity develop independently of CD4 help |
| title_sort | tumor resident memory cd8 t cells and concomitant tumor immunity develop independently of cd4 help |
| url | https://doi.org/10.1038/s41598-023-33508-1 |
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