Figure 1.

Immunosurveillance, evasion, and tolerance in cancer. Innate and adaptive immune systems work in consortium to eliminate cancer cells before their clinical appearance (A). Innate immune cells (NK) interact with neoplastic cells through their surface receptors (NKG2D, NKp30, NKp44, NKp46, CD16) and kill them by (i) release of cytotoxic granules (perforin, granzyme) in the vicinity; (ii) death (TNF, FasL, TRAIL) receptor-mediated apoptosis; and (iii) secretion of IFN-ϒ which inhibits proliferation of tumor cells by activating M1 macrophages (Mϕ) and DCs as well as Th1 cells of adaptive immune system. Dendritic cells (DCs), recruited at the tumor site, present tumor-specific antigens released by tumor killing. Antigen presenting DCs interact with naive T-cells in tumor draining lymph nodes facilitating clonal expansion of CD4+ and CD8+ T-cells which then differentiate into antigen-specific effector T-cells: T-helper cells (Th1, Th2, Th17) and cytotoxic T-cell lymphocytes (CTL), respectively. DCs also control the humoral part of adaptive immunity either by directly interacting with B cells or through CD4⁺ helper T-cell by differentiating B cells into antibody secreting cells. In addition to immune surveillance failure, cancer progress by evading immune attack (B). Immune pressure selects poorly immunogenic tumor cells, not recognized by effector cells of innate and adaptive immunity. These immune-evasive cells modulate TME further to make it more immunosuppressive by activating accessory cells: regulatory T-cells (T-regs), tumor-associated macrophages (TAMs), regulatory dendritic cells (reg-DCs), and myeloid-derived suppressor cells (MDSCs). The combined activity of these immune suppressor cells regulates tumor growth, survival, migration, and invasion by changing the hormone, growth factor, and cytokine profile of TME. Levels of cytokines involved in immune suppression and evasion and which are higher in AA are highlighted in red.