The ability of tumors to evade being recognized by the immune system plays a critical role in cancer progression. Now, as discussed in the current issue of the Journal of Clinical Investigation, Gerard Blobe, M.D., Ph.D., and a team at Duke University have explored the tumor microenvironment and identified a mechanism by which tumors evade detection.
Using mouse models of breast cancer and melanoma, they show that loss of the Type III TGF-β receptor (TGFBR3) in tumors promotes cancer progression by altering signaling in tumor-associated immune cells. The scientists say their study also supports the use of TGF-β inhibitors to enhance the efficacy of therapies that promote immune-mediated elimination of tumor cells.
According to the researchers, TGFBR3 and its shed extracellular domain (sTGFBR3) regulate signaling pathways involving TGF-β. Epithelial homeostasis is thus maintained. As previously noted, they cite the loss of TGFBR3 expression as a key factor in the progression of breast cancer in its early stages.
Work with the murine models demonstrated that the loss of tumor-expressed TGFBR3/sTGFBR3 enhanced TGF-β signaling within locoregional dendritic cells (DC). “Alterations in these DC populations mediated Treg [regulatory T cell] infiltration and the suppression of antitumor immunity,” wrote the scientists.
The researchers concluded that if TGF-β expression is inhibited, this would provide a novel method of tumor immunotherapy and that “sTGFBR3 levels could serve as a predictive immunotherapy biomarker.”