Whole body irradiation increases the magnitude and persistence of adoptively transferred T cells associated with tumor regression in a mouse model of prostate cancer
Menée sur un modèle murin d'adénocarcinome de la prostate, cette étude met en évidence l'intérêt d'une radiothérapie de l'ensemble du corps pour améliorer, dans le cadre d'une immunothérapie adoptive, la persistance et l'amplification des cellules T CD8+ transférées
Adoptive immunotherapy has demonstrated efficacy in a subset of clinical and preclinical studies, but the T cells used for therapy are often rapidly rendered non-functional in tumor-bearing hosts. Recent evidence indicates that prostate cancer can be susceptible to immunotherapy, but most studies using autochthonous tumor models demonstrate only short-lived T cell responses in the tolerogenic prostate microenvironment. Here, we assessed the efficacy of sublethal whole body irradiation (WBI) to enhance the magnitude and duration of adoptively transferred CD8+ T cells in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. We demonstrate that WBI promoted high-level accumulation of granzyme B (GzB)-expressing donor T cells both in lymphoid organs and the prostate of TRAMP mice. Donor T cells remained responsive to vaccination in irradiated recipients, but a single round of WBI-enhanced adoptive immunotherapy failed to significantly impact existing disease. Addition of a second round of immunotherapy promoted regression of established disease in half of the treated mice, with no progressions observed. Regression was associated with long-term persistence of effector/memory phenotype CD8+ donor cells. Administration of the second round of adoptive immunotherapy led to reacquisition of GzB expression by persistent T cells from the first transfer. These results indicate that WBI conditioning amplifies tumor-specific T cells in the TRAMP prostate and lymphoid tissue, and suggest the initial treatment alters the tolerogenic microenvironment to increase anti-tumor activity by a second wave of donor cells.