Co-administration of a clinically relevant dexamethasone dosage with ablative radiotherapy reduces peripheral lymphocytes but does not alter in vivo intratumoral lymphocyte phenotype or inhibit efficacy of radiotherapy in a murine colorectal tumor model.

Abstract Purpose Dexamethasone is commonly given during radiotherapy (RT) to manage toxicities. Our study examines if dexamethasone co-administration with RT inhibits the RT-induced anti-tumor T cell response in mouse. Materials and Methods Intramuscularly implanted MC38 tumors were irradiated with 15 Gy after establishing for 7 days. Tumor bearing mice were administered dexamethasone using multiple schedules and doses. Peripheral lymphocyte reduction was monitored by complete blood count and intratumoral and tumor draining lymph node (tdLN) populations by flow cytometry. Effector phenotype and function of ex vivo stimulated tumor-infiltrating lymphocytes (TILs) and naive splenocytes as well as in vivo TILs with or without dexamethasone were monitored by flow cytometry and ELISA. Results Long course high dose, short course high dose, and short course human equivalent (HE) dose dexamethasone reduced peripheral lymphocytes yet did not inhibit survival following irradiation. Short course high dose administration decreased TIL and tdLN lymphocyte activation as well as tdLN mass but did not affect TIL frequencies or change tdLN cell population composition. Dexamethasone inhibited effector function of ex vivo stimulated naive splenocytes and TILs, but magnitude of IFN-γ secretion was consistently higher in TILs regardless of dexamethasone dose. In vivo analysis of TILs following irradiation and HE dexamethasone treatment showed that TILs had a similar effector phenotype compared to vehicle controls. Conclusions Dexamethasone reduces blood and tdLN lymphocytes. Dexamethasone also suppresses TIL activation/effector function yet does not affect survival in irradiated MC38 tumor bearing mice, which depend on RT-induced immune responses for therapy efficacy. Additional study in human subjects is warranted.