Immunological hallmarks of stromal cells in the tumour microenvironment

Non-haematopoietic stromal cells in the tumour microenvironment actively interact with infiltrating leukocytes. Emerging evidence also suggests that the stromal compartment can shape antitumour immunity and responsiveness to immunotherapy.Dysfunctional endothelial cells and aberrant pericyte coverage in tumour blood vessels results in tortuous and leaky vessels, which greatly impinge on leukocyte infiltration. Diapedesis of effector immune cells is further limited by the reduced expression of endothelial adhesive molecules.Fibroblasts contribute to shaping the immune cell populations in tumours by secreting chemokines that can selectively repel effector T cells while favouring the recruitment of immunosuppressive cells.Stromal cells in the tumour microenvironment can also actively hinder antitumour immunity by several mechanisms, including expression of inhibitory receptors, production of molecules that induce T cell apoptosis and secretion of immunosuppressive factors.Overcoming immune suppression is of the upmost importance for cancer treatment. In light of the increasing evidence that suggests a role for the tumour stroma in limiting antitumour immune responses, we anticipate that therapies targeting stromal cells in the tumour microenvironment will be likely to provide enormous benefits.