Fig. 3

Illustration of the mechanism-based application of immunotherapies with LDRT. The release of tumor-associated antigens by high-dose radiation therapy (HDRT) or chemotherapy initiates T-cell priming, further amplified by enhanced T-cell infiltration to metastatic sites using low-dose radiation therapy (LDRT). At this stage, combining immunotherapies with LDRT can be particularly beneficial. The release of chemokines, stromal modulation, and further boosting of T cell priming enhance the effects of ICI (anti-PD1 plus anti-CTLA-4). Additionally, the increased infiltration of T and NK cells helps harness the synergistic effects of adoptive cell therapy (ACT) when combined with LDRT. Moreover, LDRT can convert M2 tumor-associated macrophages (TAMs) to the antitumor M1 type. This also explains the positive abscopal antitumor immune responses observed at metastatic sites when using LDRT combined with immunotherapies