Figure 2.

Immune modifying effects of radiotherapy (RT) and immune-checkpoint blockade (ICB). (Left panel) Immune responses induced by radiotherapy (RT): Initial (1°C) anti-tumor immune response includes (A) increased pool of tumor antigens and DAMPs which results in antigen presentation activity, (B) subsequent activation of T cells and enhanced infiltration of anti-tumor immune cells into the TME to facilitate tumor-killing; Secondary (2°C) wave of immunosuppressive response is denoted by (C) recruitment of immunosuppressive immune subsets, Tregs and TAMs and (D) upregulated expression of immune checkpoint molecules by tumor cells (PD-L1) and cytotoxic CD8+ T cells (PD-1 and CTLA-4) which dampens anti-tumor activity. (Right panel) Immune responses mediated by immune checkpoint blockade (ICB): (A) Anti-PD-1 and anti-PD-L1 interferes with PD-1/PD-L1 interaction and relieves suppression of CD8+ T cells by tumor cells. (B) Anti-CTLA-4 blocks inhibitory signaling by inhibiting B7/CTLA-4 binding and allows for the activation of APCs and T cells. (Bottom panel) Potential synergistic effects of combining RT and ICB include enhanced infiltration of anti-tumor into TME post-RT and reversion of radiation-induced exhaustion and immunosuppression by ICB.