Figure 1.

Key immune cell subsets in breast cancer tumor microenvironment. The production of IFNγ by CD4+ Th1 cells mediates the expansion, differentiation and activation of CD8+ tumor-infiltrating lymphocytes (TILs), which subsequently release cytotoxic cytokines and directly kill cancer cells (via recognition of specific tumor-associated antigens on the surface of antigen presentation cells (APCs) or cancer cells); CD4+FOXP3+ TILs represent immunosuppressive mediators through the inhibition of CD8+ T cells, CD4+ Th1 cells, APCs and natural killer cells (NKs); M1 tumor-associated macrophages (M1-TAMs) are associated with Th1 cytotoxic immune response, thus exhibiting antitumor properties; M2-TAMs contribute to the activation of Th2 immune response, thus showing an immunosuppressive role (e.g., suppression of T cell function); NKs are cytotoxic members of the innate immune system (release of cytotoxic cytokines and direct killing of cancer cells); dendritic cells (DCs) are antigen-presenting cells and are crucial players of the adaptive immune system; myeloid-derived suppressor cells (MDSCs) represent immature myeloid cells (possibly originated from bone marrow precursors) with an immunosuppressive function via the inhibition of T cells, B cells, NKs, M1-TAMs and DCs. The recruitment and accumulation of immunosuppressive mediators into the tumor bed is mediated by the secretion of cytokines and chemokines (e.g., IL6, IL1-β, TGF-1β, CCL2) by tumor cells. Red and green arrows reflect inhibitory and stimulatory relationships, respectively. Abbreviations: IFNγ, interferon gamma; TILs, tumor-infiltrating lymphocytes, APCs, antigen presentation cells, NKs, natural killer cells, DCs, dendritic cells, TAMs, tumor-associated macrophages; MDSCs, myeloid-derived suppressor cells; TLS, tertiary lymphoid structure.