Despite the increasing interest in targeting stromal elements of the tumor microenvironment, we still face tremendous challenges in developing adequate therapeutics to modify the tumor stromal landscape. The biggest obstacle is represented by our poor understanding of the phenotypic and functional heterogeneity of stromal cells in tumors. Our work aims at addressing some of this ambiguity, focusing on the immunoregulatory roles exerted by specific subsets of mesenchymal cells in the tumor microenvironment.