Tumor resident memory CD8 T cells and concomitant tumor immunity develop independently of CD4 help.
Publication Title
Sci Rep
Authors
Terry R Medler, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USAFollow
Gwen Kramer, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USAFollow
Shelly Bambina, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA
Andrew J Gunderson, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA
Alejandro Alice, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USAFollow
Tiffany Blair, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA
Lauren Zebertavage, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA
Thomas Duhen, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USAFollow
Rebekka Duhen, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA
Kristina Young, 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.Follow
Marka R Crittenden, 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.Follow
Michael J Gough, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USAFollow
Publication Date
4-18-2023
Keywords
oregon; chiles; portland
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.
Clinical Institute
Cancer
Specialty/Research Institute
Oncology
Specialty/Research Institute
Earle A. Chiles Research Institute
DOI
10.1038/s41598-023-33508-1
