Tumor resident memory CD8 T cells and concomitant tumor immunity develop independently of CD4 help.

Autor: Medler TR; Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA., Kramer G; Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA., Bambina S; Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA., Gunderson AJ; Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA.; Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The OH State University, Columbus, OH, 43210, USA., Alice A; Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA., Blair T; Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA., Zebertavage L; Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA., Duhen T; Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA., Duhen R; Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA., Young K; Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA.; The Oregon Clinic, Portland, OR, 97213, USA., Crittenden MR; Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA.; The Oregon Clinic, Portland, OR, 97213, USA., Gough MJ; Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA. michael.gough@providence.org.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Apr 18; Vol. 13 (1), pp. 6277. Date of Electronic Publication: 2023 Apr 18.
DOI: 10.1038/s41598-023-33508-1
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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