Development of personalized combination cancer immunotherapy based on the patients’ immune status

Abstract

Cancer immunotherapies, particularly immune-checkpoint blockade and T cell-based adoptive cell therapy, have recently been recognized as cancer treatments that show strong and durable responses even for advanced cancer patients with multiple metastases. The major issues in the development of cancer immunotherapy are the identification of biomarkers to distinguish responders and nonresponders, and the improvement of efficacy of immunotherapy possibly by combination with appropriate immune interventions targeting different key regulating points in the anti-tumor immune responses. Interestingly, pretreatment T cell immune status varies among cancer patients, and appears to correlate with responses to various cancer treatments including surgery, chemotherapy, radiation therapy, and immunotherapy. Balance of anti-tumor T cell induction pathway and immunosuppressive pathway, which are regulated by characteristics of both cancer cells and patients’ immune reactivity, may define the differential immune status among cancer patients along with environmental factors such as intestinal microbiota. The analysis of such mechanisms may lead to the identification of immune biomarkers and immune-modulating strategies for combination immunotherapies. Further research on human cancer immunopathology will lead to the development of effective personalized combination immunotherapies based on the evaluation of cancer patients’ immune status.