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. 2017 Jan 9;7:682. doi: 10.3389/fimmu.2016.00682

Figure 2.

Figure 2

Role of interleukin-33 (IL-33) in the tumor microenvironment. (A) In breast cancer (mouse 4T1 breast cancer model), IL-33 is released by tumor cells and acts in an autocrine/paracrine manner. In addition, IL-33 promotes the recruitment of immunosuppressive cells and inhibits the function of antitumor cytotoxic natural killer cells (NK). (B) In gastric cancer, IL-33 may promote vessel invasion of tumor cells by stimulating the secretion of IL-6 and MMP-3 through activation of the ERK pathway. (C) In colorectal cancer, IL-33 supports the recruitment to the tumor environment of pro-tumorigenic immune cells, including mast cells and myeloid-derived suppressor cells (MDSCs). In addition, IL-33 promotes the secretion of pro-tumorigenic IL-6 by leukocytes in the tumor vicinity, which are possibly CD11c+ dendritic cells. (D) In patients with myeloproliferative neoplasms, IL-33 is released by bone marrow stromal and endothelial cells, and it engages ST2 on CD34+ hematopoietic stem/progenitor cells, thereby promoting their secretion of IL-6 and GM-CSF. These cytokines, in turn, stimulate in an auto/paracrine manner the uncontrolled proliferation of the malignant clone (due to its defect in JAK/STAT signaling).