Fluorescence tracking identifies T cell movement from lymph nodes to irradiated tumors and mechanisms of T cell retention during post-radiation refilling 3240

Description Radiation therapy (RT) is a potent mediator of cancer cell death, but normal cells including T cells are killed in the treatment field. In this work we use the photoconvertible Kaede mouse model to identify cells that move from the tumor-draining lymph node (TdLN) to untreated (NT) and RT treated tumors in mice. We demonstrate selective recruitment of effector and memory CD8 T cells from the TdLN to tumors. By uniquely focusing on the recruited cells we see enrichment for progenitor exhausted cells in both NT and RT tumors, but over time their activation is distinct in RT tumors. RT results in upregulation of the activation/retention marker CD69 particularly in progenitor exhausted cells during the early phase of RT tumor refilling. Using irrelevant antigen vaccination, we demonstrate that CD69 upregulation is antigen non-specific. Tumors grown in IFNAR1-/- mice reveal that CD69 upregulation is IFN-mediated, resulting from RT-mediated adjuvant signaling in the irradiated tumors. scRNASeq analysis of photoconverted versus resident T cells demonstrates the distinct tumor environment of irradiated tumors redirects newly entered T cell differentiation. These data demonstrate an initial non-specific retention prior to antigen-specific engagement contributes to refilling of irradiated tumors with implications for therapy. Funding Sources This research was funded by NCI R01CA182311, NCI R01CA244142, and R01CA208644, and by the Providence Foundation. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)