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

Document Type

Article

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.

Area of Special Interest

Cancer

Specialty/Research Institute

Oncology

Specialty/Research Institute

Earle A. Chiles Research Institute

DOI

10.1038/s41598-023-33508-1