Low-Dose Irradiation Programs Macrophage Differentiation to an iNOS+/M1 Phenotype that Orchestrates Effective T Cell Immunotherapy (original) (raw)

“…The possible mechanisms undergirding these findings are that radiotherapy upregulates tumor-associated antigen-MHC complexes, enhances antigen cross-presentation in the draining lymph node, boosts T cell infiltration into tumors, 42 and promotes tumor-associated macrophage transformation from M2 to M1. 43 At the same time, emerging evidences indicated that low doses of fractionated radiotherapy led to PD-L1 upregulation on tumor cells by recruiting infiltrated lymphocytes in an IFNg-dependent manner, and fractionated radiotherapy delivered in combination with anti PD-1 or anti PD-L1 mAbs generated efficacious CD8 C T-cell responses that improved local tumor control, long-term survival, and protection against tumor re-challenge. 44,45 Although we showed that the PD-1-disrupted LMP2A-CTLs conferred enhanced cytotoxicity to the EBV-positive gastric cancer cell line in vitro, in the xenograft model of EBVaGC, we did not observe augmented tumor regression following treatment of PD-1 disrupted LMP2A-CTL.…”