Modulation of Lymphocyte Functions in the Microenvironment by Tumor Oncogenic Pathways

Abstract

Despite the broad application of different immunotherapeutic strategies for the treatment of solid as well as hematopoietic cancers, the efficacy of these therapies is still limited, with only a minority of patients having a long-term benefit resulting in an improved survival rate. In order to increase the response rates of patients to the currently available immunotherapies, a better understanding of the molecular mechanisms underlying the intrinsic and/or extrinsic resistance to treatment is required. There exist increasing evidences that activation of different oncogenic pathways as well as inactivation of tumor suppressor genes (TSG) in tumor cells inhibit the immune cell recognition and influegnce the composition of the tumor microenvironment (TME), thus leading to an impaired anti-tumoral immune response. A deeper understanding of the link between the tumor milieu and genomic alterations of TSGs and oncogenes is indispensable for the optimization of immunotherapies and to predict the patients' response to these treatments. This review summarizes the role of different cancer-related, oncogene- and TSG-controlled pathways in the context of anti-tumoral immunity and response to different immunotherapies.

Keywords: immunotherapy; oncogenic pathways; tumor; tumor infiltrating lymphocytes; tumor suppressor genes.