Ex vivo tumor explant analyses reveal suppression of tumor-infiltrating T cells, but not myeloid cells, post radiation treatment
oregon; portland; chiles
"Radiotherapy as a cancer treatment strategy is also known for its ability to modulate the immunogenicity of tumors, with the potential of reshaping the immune context of tumors to favor antitumor adaptive immune responses. The immune response to radiotherapy is crucial in deciding the fate of residual disease. While the direct impact of radiation on immune cells can be followed in preclinical models, repeated sampling is problematic in patients and the simultaneous evaluation of radiation dosing and fractionation options within one individual is not possible. To study and characterize the immune cell subsets in tumors following radiation therapy, we developed an ex vivo tumor explant assay that maintains tissue architecture and allows experimental evaluation of the tumor in isolation. We hypothesized a decline in the proportion of radiosensitive T cell subsets in tumor explants following ex vivo radiation therapy but not in the myeloid population. Tumor explants derived from C57BL/6 mice were either exposed to 12 Gy of radiation or left untreated and were processed after two days of incubation for final analysis using flow cytometry. The effect of radiation treatment on the frequency of T cells and CD11b+ myeloid cells in the tumor explants was assessed. Our analysis showed a significant decrease (p<0.05) in the proportion of T cells in the irradiated tumors while the proportion of CD11b+ myeloid cells remained unchanged. We validate these data in patient tumors from a range of malignancies and explore the dose sensitivity of T cell subsets in tumors. Our study characterizes the use of tumor explants to evaluate the patient-specific response to radiation therapy that could potentially be used as a predictor of treatment outcome. While explants are limited to the study of pre-existing immune responses infiltrating tumors, it can be developed as a screening tool to rapidly identify from a large pool of options, patient-specific immunotherapies for combination with optimized radiation."
Kaur, AP; Kramer, G; Crittenden, MR; and Gough, MJ, "Ex vivo tumor explant analyses reveal suppression of tumor-infiltrating T cells, but not myeloid cells, post radiation treatment" (2022). Articles, Abstracts, and Reports. 6981.
Radiation Research Society Annual Meeting; October 16-19; Waikoloa Village, HI. 2022.