Fluorescence tracking demonstrates T cell recirculation is transiently impaired by radiation therapy to the tumor.
Publication Title
Sci Rep
Document Type
Article
Publication Date
5-24-2024
Keywords
oregon; chiles; Animals; Mice; CD8-Positive T-Lymphocytes; Lymph Nodes; Lymphocytes, Tumor-Infiltrating; Neoplasms; Cell Tracking; Cell Line, Tumor; Mice, Inbred C57BL; Fluorescence
Abstract
T cells recirculate through tissues and lymphatic organs to scan for their cognate antigen. Radiation therapy provides site-specific cytotoxicity to kill cancer cells but also has the potential to eliminate the tumor-specific T cells in field. To dynamically study the effect of radiation on CD8 T cell recirculation, we used the Kaede mouse model to photoconvert tumor-infiltrating cells and monitor their movement out of the field of radiation. We demonstrate that radiation results in loss of CD8 T cell recirculation from the tumor to the lymph node and to distant sites. Using scRNASeq, we see decreased proliferating CD8 T cells in the tumor following radiation therapy resulting in a proportional enrichment in exhausted phenotypes. By contrast, 5 days following radiation increased recirculation of T cells from the tumor to the tumor draining lymph node corresponds with increased immunosurveillance of the treated tumor. These data demonstrate that tumor radiation therapy transiently impairs systemic T cell recirculation from the treatment site to the draining lymph node and distant untreated tumors. This may inform timing therapies to improve systemic T cell-mediated tumor immunity.
Area of Special Interest
Cancer
Specialty/Research Institute
Earle A. Chiles Research Institute
Specialty/Research Institute
Oncology
DOI
10.1038/s41598-024-62871-w
