Figure 3.

Contrasting roles of adaptive leukocytes during cancer development. During acute inflammatory responses (left panel), Th1 CD4⁺ and CD8⁺ T cells directly regulate tumor cell cytotoxicity, while indirectly polarizing innate immune cells toward tumor suppression (such as M1 polarization of tumor-associated macrophages [TAMs]). B-cell-derived factors (immunoglobulins and complement) facilitate recruitment of innate leukocytes and targeted destruction of neoplastic cells. During chronic inflammation, however (right panel), myeloid suppressor cells, Th2 CD4⁺ T cells and regulatory T (T-reg) cells function in combination to both repress CD8⁺ cytotoxicity and to induce protumoral polarization of innate immune response (such as M2 polarization of TAMs) via cytokine secretion (IL-4, IL-13, IL-10, IL-6 and transforming growth factor beta (TGFβ)). Chronically activated B cells promote accumulation of innate cells in the neoplastic stroma by immunoglobulin and cytokine production. When polarized, as during chronic inflammation, these innate immune cells in turn provide a rich proangiogenic and protumoral microenvironment. CTL, cytotoxic T lymphocyte; FcR, Fc receptor; INF, interferon; SC, suppressor cells; VEGF, vascular endothelial growth factor.