Enabling CAR-T cells for solid tumors: Rage against the suppressive tumor microenvironment

Adoptive T cell therapies based on chimeric antigen receptors (CAR-T) are emerging as genuine therapeutic options for the treatment of hematological malignancies. The observed clinical success has not yet been extended into solid tumor indications as a result of multiple factors including immunosuppressive features of the tumor microenvironment (TME). In this context, an emerging strategy is to design CAR-T cells for the elimination of defined cellular components of the TME, with the objective of re-shaping the tumor immune contexture to control tumor growth. Relevant cell components that are currently under investigation as targets of CAR-T therapies include the tumor vasculature, cancer-associated fibroblasts (CAFs), and immunosuppressive tumor associated macrophages (TAMs) and myeloid derived suppressor cells (MDSCs). In this review, we recapitulate the rapidly expanding field of CAR-T cell therapies that directly target cellular components within the TME with the ultimate objective of promoting immune function, either alone or in combination with other cancer therapies.