Figure 1.

Simplified overview of immune surveillance and tumor evasion in pancreatic ductal adenocarcinoma (PDA). Immune surveillance is the process whereby the immune system surveys the body for malignant or infected cells. Components of immune surveillance include T cells, DCs, NK cells, and macrophages (TAM). Mutations in oncogene KRAS are a driver of PDA. The immune response to transformed tissue can either result in complete elimination of the malignancy, equilibrium to prevent further growth of the malignancy, or escape and development of clinically significant tumors. This figure provides a hypothesized sequence of immune evasion, but this process is likely not linear and instead a dynamic progression. Cancer cells can escape T cell recognition by losing target antigen expression and/or developing defects in antigen processing and presentation. Additionally, defects in T cell priming or trafficking to tumors may limit antigen-specific T cell responses and can be attributed to insufficient mature DCs. When antigen-specific T cells successfully infiltrate tumors, their function may be limited by immunosuppressive cytokines produced by macrophages (TAM, tumor-associated macrophage), regulatory T cells (Treg), myeloid-derived suppressor cells (MDSC), or cancer associated fibroblasts (CAF). Lastly chronic T cell receptor signaling drives T cell exhaustion, resulting in reduced effector function.