Fig. 1.

The tumor immune microenvironment (TIME), and the effects of radiation and immunotherapy thereon.A) The tumor immune microenvironment, consisting of various cell types including cancer and immune subpopulations, some of which are shown. Interactions within the TIME include the uptake and processing of tumor associated antigen (TAA) by professional antigen presentation cells (APC) such as dendritic cells; the influx of TAA specific activated T cells, the recognition and lysis of cancer cells. Additionally, activated T cells can be regulated and suppressed by T-reg cells or tumor cells via the PD-1:PD-L1 axis or CTLA-4, and macrophages can phagocytose cancer cells. B-C) Interactions within the TIME can be generalized as occurring between six compartments: cancer cells, doomed cancer cells, TAA, APCs, effector immune cells, and regulatory immune cells. Black arrows denote these interactions, with inhibitory interactions shown as blocked arrows, and stimulatory interactions indicated by sharp arrows. Administration of (B) radiotherapy and (C) immunotherapy affect these interactions in different ways, detailed reviews of which can be found elsewhere [45,151]. Figures created with BioRender (www.biorender.com).