Immunological hallmarks of stromal cells in the tumour microenvironment

• Published in: Nature reviews. Immunology Vol. 15; no. 11; pp. 669 - 682
• Main Authors: Turley, Shannon J., Cremasco, Viviana, Astarita, Jillian L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2015; Nature Publishing Group
• Subjects: 631/250/2520; 631/250/580; 631/67/327; Adipocytes; Animals; Antigens; Biomedicine; Cancer; Care and treatment; Cell Communication; Cell Movement; Cytotoxicity, Immunologic; Dendritic cells; Extracellular matrix; Extracellular Matrix - physiology; Fibroblasts; Fibroblasts - physiology; Growth factors; Health aspects; Humans; Immunology; Immunotherapy; Leukocytes; Leukocytes - physiology; Lymphatic system; Medical prognosis; Mesenchymal Stromal Cells - physiology; review-article; Stem cells; Stromal Cells - immunology; Tumor Microenvironment; Tumors; United States; United States > US; Massachusetts
• ISSN: 1474-1733; 1474-1741
• DOI: 10.1038/nri3902

Key Points 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. Emerging evidence suggests that the stroma of the tumour microenvironment can shape antitumour immunity and responsiveness to immunotherapy. The stromal cells and the signals they produce that influence tumour-infiltrating leukocytes, as well as the implications for cancer treatment, are reviewed here. A dynamic and mutualistic interaction between tumour cells and the surrounding stroma promotes the initiation, progression, metastasis and chemoresistance of solid tumours. Far less understood is the relationship between the stroma and tumour-infiltrating leukocytes; however, emerging evidence suggests that the stromal compartment can shape antitumour immunity and responsiveness to immunotherapy. Thus, there is growing interest in elucidating the immunomodulatory roles of the stroma that evolve within the tumour microenvironment. In this Review, we discuss the evidence that stromal determinants interact with leukocytes and influence antitumour immunity, with emphasis on the immunological attributes of stromal cells that may foster their protumorigenic function.