Immune Therapy Resistance and Immune Escape of Tumors

SIMPLE SUMMARY: The genetic adaptability of malignant cells and their consequent heterogeneity even within the same patient poses a great obstacle to cancer patient treatment. This review summarizes the data obtained in the last decade on different preclinical mice models as well as on various immunotherapeutic clinical trials in distinct solid and hematopoietic cancers on how the immune system can be implemented in tumor therapy. Moreover, the different intrinsic and extrinsic escape strategies utilized by the tumor to avoid elimination by the immune system are recapitulated together with the different approaches proposed to overcome them in order to succeed and/or to enhance therapy efficacy. ABSTRACT: Immune therapy approaches such as checkpoint inhibitors or adoptive cell therapy represent promising therapeutic options for cancer patients, but their efficacy is still limited, since patients frequently develop innate or acquired resistances to these therapies. Thus, one major goal is to increase the efficiency of immunotherapies by overcoming tumor-induced immune suppression, which then allows for immune-mediated tumor clearance. Innate resistance to immunotherapies could be caused by a low immunogenicity of the tumor itself as well as an immune suppressive microenvironment composed of cellular, physical, or soluble factors leading to escape from immune surveillance and disease progression. So far, a number of strategies causing resistance to immunotherapy have been described in various clinical trials, which broadly overlap with the immunoediting processes of cancers. This review summarizes the novel insights in the development of resistances to immune therapy as well as different approaches that could be employed to overcome them.