Regulatory dendritic cells in the tumor immunoenvironment.

The tumor microenvironment is a pivotal factor in tumorigenesis, and especially in progression, as the pathogenesis of cancer critically depends on the complex interactions between various microenvironmental components. A key component of the tumor immunoenvironment is the infiltration of immune cells, which has been proven to play a dual role in tumor growth and progression. This Janus two-faced function of the tumor immunoenvironment is seen in tumor infiltration by T cells, which correlates with improved patient survival, but also with the homing of multiple subsets of immunoregulatory cells that inhibit the antitumor immune response. Regulatory dendritic cells (regDCs) have recently been shown to be induced by tumor-derived factors and represent a new and potentially important player in supporting tumor progression and suppressing the development of antitumor immune responses. Our recent data reveal that different tumor cell lines produce soluble factors that induce polarization of conventional DCs into regDCs, both in vitro and in vivo. These regDCs can suppress the proliferation of pre-activated T cells and are phenotypically and functionally different from their precursors as well as the classical immature conventional DCs. Understanding the biology of regDCs and the mechanisms of their formation in the tumor immunoenvironment will provide a new therapeutic target for re-polarizing protumorigenic immunoregulatory cells into proimmunogenic effector cells able to induce and support effective antitumor immunity.