Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy.

ABSTRACT: Developing strategies to inflame tumors is critical for increasing response to immunotherapy. Here, we report that low-dose radiotherapy (LDRT) of murine tumors promotes T-cell infiltration and enables responsiveness to combinatorial immunotherapy in an IFN-dependent manner. Treatment efficacy relied upon mobilizing both adaptive and innate immunity and depended on both cytotoxic CD4⁺ and CD8⁺ T cells. LDRT elicited predominantly CD4⁺ cells with features of exhausted effector cytotoxic cells, with a subset expressing NKG2D and exhibiting proliferative capacity, as well as a unique subset of activated dendritic cells expressing the NKG2D ligand RAE1. We translated these findings to a phase I clinical trial administering LDRT, low-dose cyclophosphamide, and i

SUBMITTER: Herrera FG 

PROVIDER: S-EPMC9401506 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature