Tumor-intrinsic signaling pathways: key roles in the regulation of the immunosuppressive tumor microenvironment

• Main Authors: Li Yang, Aitian Li, Qingyang Lei, Yi Zhang
• Format: Article
• Language: English
• Published: BMC 2019-11-01
• Series: Journal of Hematology & Oncology
• Subjects: Immunosuppressive tumor microenvironment; Immune escape; T cell infiltration; Immunosuppressive cells; Tumor-intrinsic signaling
• Online Access: http://link.springer.com/article/10.1186/s13045-019-0804-8

Abstract Immunotherapy is a currently popular treatment strategy for cancer patients. Although recent developments in cancer immunotherapy have had significant clinical impact, only a subset of patients exhibits clinical response. Therefore, understanding the molecular mechanisms of immunotherapy resistance is necessary. The mechanisms of immune escape appear to consist of two distinct tumor characteristics: a decrease in effective immunocyte infiltration and function and the accumulation of immunosuppressive cells in the tumor microenvironment. Several host-derived factors may also contribute to immune escape. Moreover, inter-patient heterogeneity predominantly results from differences in somatic mutations between cancers, which has led to the hypothesis that differential activation of specific tumor-intrinsic pathways may explain the phenomenon of immune exclusion in a subset of cancers. Increasing evidence has also shown that tumor-intrinsic signaling plays a key role in regulating the immunosuppressive tumor microenvironment and tumor immune escape. Therefore, understanding the mechanisms underlying immune avoidance mediated by tumor-intrinsic signaling may help identify new therapeutic targets for expanding the efficacy of cancer immunotherapies.