Soluble Mediators of Immune Suppression in the Tumor Microenvironment

Malignant transformation of cells produces radical changes in their metabolism and the soluble factors they produce. These changes support rapid cell proliferation and facilitate their invasion into surrounding tissues as well as distant metastatic spread. The type of soluble factors produced by tumors and their effect on the immune response can be divided into those that directly impair antitumor protective functions of T cells, and those that induce the production of high number of immature myeloid cells from the bone marrow that migrate to the tumor microenvironment (TME). Under normal conditions these cells are essential for tissue repair but in the TME they become chronic inflammatory cells that are potent inhibitors of T cells and NK cells. Multiple approaches are currently being tested in animal models and in patients to overcome these powerful mechanisms and allow the induction of a protective and therapeutic antitumor immune response.