Session Item

Therapeutic monoclonal antibodies that block various immune checkpoints have shown efficacy against a wide range of solid tumors. One of the primary resistance mechanisms to immune checkpoint inhibitor (ICI)-based therapies is the exclusion or absence of lymphocytes within the tumor microenvironment (TME). As a result, there is a growing interest in developing novel strategies to promote T cell infiltration on immune-depleted (cold) and immune-excluded tumors in order to convert them to inflamed (hot) tumors. I will present a comprehensive review of recent studies demonstrating the potential of low-dose radiation (LDRT) to reprogram the TME to allow and promote T-cell infiltration, thereby improving currently approved ICI-based therapies. I will present new scRNAseq data on the mechanisms of resistance to LDRT and briefly summarize our experience in characterizing the mechanisms that are central to low dose irradiation to increase T cell infiltration in mice and patients. Finally, based on these findings, I will discuss future clinical trial designs combining low-dose irradiation and immunotherapy.