Investigating tumor immunogenicity as a determinant of differential abscopal effects

Abstract

This study investigated the role of tumor immunogenicity in the ionizing radiation (IR)-induced abscopal effect. The ovalbumin-expressing B16 cell line (B16-OVA) served as a relatively immunogenic tumor model compared to the B16F10 cell line. C57BL/6 mice were implanted with B16-OVA or B16F10 in the left thigh as the primary tumor and B16F10 in the right thigh as the secondary tumor to evaluate the abscopal response. IR was applied solely to the primary tumor, followed by administration of isotype or anti-programmed cell death protein-1 (PD-1) antibodies. Tumor-infiltrating immune cells were analyzed using flow cytometry. B16-OVA tumors exhibited increased T-cell infiltration and elevated granzyme B and Ki-67 expression in CD8+ T cells compared to B16F10 tumors. IR delayed secondary tumor growth in B16-OVA-irradiated mice, but not in B16F10-irradiated mice. While CD8+ T-cell numbers increased in the secondary tumors of both groups, regulatory T cells significantly increased only in B16F10-irradiated mice. IR promoted differentiation from stem-like TCF1+TIM3- to effector-like TCF1-TIM3+ CD8+ T cells, with elevated granzyme B expression. Polyfunctional T cells co-expressing IFN-γ, TNF-α and IL-2 were significantly increased only in secondary tumors of B16-OVA-irradiated mice under PD-1 blockade. The abscopal effect was abolished by FTY720 treatment and CD8+ T-cell depletion. In conclusion, the IR-induced abscopal effect was dependent on the immunogenicity of the irradiated tumor. The findings may have implication on enhancing abscopal effect in clinical settings.