Fluorescence tracking demonstrates T cell recirculation is transiently impaired by radiation therapy to the tumor

Author:

Kramer Gwen,Blair Tiffany,Bambina Shelly,Kaur Aanchal Preet,Alice Alejandro,Baird Jason,Friedman David,Dowdell Alexa K.,Tomura Michio,Grassberger Clemens,Piening Brian D.,Crittenden Marka R.,Gough Michael J.

Abstract

AbstractT 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.

Funder

National Cancer Institute

Publisher

Springer Science and Business Media LLC

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