Phenotypic Plasticity, Non-genetic Mechanisms, and Immune Drug Resistance in Cancer

Cancer immunotherapy is a major advancement in the field. It works by stimulating the patient's immune system to recognize and destroy cancer cells. Several different types of cancer immunotherapies have been developed, such as T-cell therapy, immune checkpoint inhibitors, monoclonal antibodies, cancer vaccines, and many others, which can result in sustainable responses in patients with a wide range of metastatic diseases. Additionally, immunotherapy drugs are being combined with chemotherapy and other targeted therapies to treat a variety of cancer types. Despite the promising results, several challenges remain, such as the almost inevitable immune resistance, drug-related toxicity, and the lack of established and reliable predictive biomarkers to predict toxicity and/or discern a patient's response to immunotherapy. In this chapter, we summarize the mechanisms underlying cancer immunotherapy resistance, especially the contributions of phenotypic plasticity and the underlying non-genetic mechanisms. Furthermore, recent developments in preventing relapses following treatment so that the efficacy of immunotherapy can be improved are also briefly discussed. Finally, the positive impact of an interdisciplinary "Team Medicine" approach to personalize cancer immunotherapy for each patient is highlighted.