Figure 2.

Key immune stimulatory and immunosuppressive events associated with IR treatment in cancer. Following IR, ICD results in the release of DAMPs, cytokines, chemokines and tumor antigens which activate APCs and induce the mass infiltration of myeloid and lymphoid cells. Three key immunological events occur following ICD which dictate the treatment response: (1) APCs internalize, process and present tumor antigens released by damaged tumor cells and migrate to the tumor draining lymph node to present these antigens to CD4⁺ and CD8⁺ T cells. (2) CD8⁺ T cells with receptors specific to the tumor antigen localize to the tumor and kill cancers via the cytolytic enzymes perforin and granzyme B, along with the cytotoxic cytokines IFN-γ and TNF-α. (3) Immunosuppressive macrophages and MDSCs suppress APC function through a variety of means, including IL-10 expression, which depletes MHC II on their surface, TGF-β, which polarizes CD4+ T cells to Tregs, Arginase, which degrades L-argining, a valuable metabolite for T cell function, and ROS, which also impair T cell function. Neutrophils also utilize arginase and ROS to mitigate T cell function.