Immunotherapy: target the stroma to hit the tumor

For decades it has been assumed that T cells reject tumors essentially by direct killing. However, solid tumors are composed of malignant cells and a variety of different nonmalignant cells, referred to as tumor stroma. Stromal cells, such as endothelial cells, fibroblasts and inflammatory cells, often support tumor growth. Here, we discuss new findings showing that the tumor stroma is an important target during T-cell-mediated tumor rejection. Cytotoxic molecules and cytokines produced by T cells inhibit or destroy the stromal ‘infrastructure’, thereby withdrawing essential resources and leading to tumor infarction and subsequent T-cell-mediated elimination of residual tumor cells. These findings are important for the development of more effective and specific immunotherapies for cancer.