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

Publication Title

Sci Rep

Authors

Gwen Kramer, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, PortlandFollow
Tiffany Blair, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, PortlandFollow
Shelly Bambina, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, PortlandFollow
Aanchal Preet Kaur, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, Portland, OR, United StatesFollow
Alejandro F Alice, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, PortlandFollow
Jason R Baird, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, PortlandFollow
David Friedman, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, Portland, OR, 97213, USA.Follow
Alexa K Dowdell, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR, USA.Follow
Michio Tomura
Clemens Grassberger
Brian D. Piening, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, Portland, OR, 97213, USA.Follow
Marka R Crittenden, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, PortlandFollow
Michael J. Gough, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, PortlandFollow

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.

Clinical Institute

Cancer

Specialty

Earle A. Chiles Research Institute

Specialty

Oncology

Recommended Citation

Kramer, Gwen; Blair, Tiffany; Bambina, Shelly; Kaur, Aanchal Preet; Alice, Alejandro F; Baird, Jason R; Friedman, David; Dowdell, Alexa K; Tomura, Michio; Grassberger, Clemens; Piening, Brian D.; Crittenden, Marka R; and Gough, Michael J., "Fluorescence tracking demonstrates T cell recirculation is transiently impaired by radiation therapy to the tumor." (2024). Articles, Abstracts, and Reports. 8935.
https://digitalcommons.providence.org/publications/8935