The morbidity of cancer is close to 50%. The emergence of cancer immunotherapy including anti-PD- (L) 1 antibody, has brought about a paradigm shift in cancer treatment. Cancer immunotherapy is expected to become more widespread as a major option for cancer treatment, but there are still several problematic issues to be solved to further expand its versatility and enhance its effectiveness. In this laboratory, Division of Clinical immunology and Cancer Immunotherapy, we are conducting researches aimed at predicting and improving so-called side reactions associated with cancer immunotherapy, immune-related adverse events (irAE). For example, if we only pay attention to the immune potentiating approaches, irAE patients will be getting increased. On the other hand, it is quite possible that systemic immunosuppression by corticosteroid attenuates anti-tumor immune responses.
If technologies to solve such seemingly contradictory issues are established, we can not only predict the safety of treatment in advance, but also rescue patients with irAE to restart cancer immunotherapy. In order to realize ideal cancer immunotherapy, it is essential to systematically understand the details of immune responses against cancer and against patients themselves (Reference Figure). Our research goals are to clarify the functional mechanisms of immune cells affected by cancer immunotherapies and to identify critical determinants for efficacy and safety of cancer immunotherapy through particularly focusing on the immunological features specific to the elderly, who account for the majority of cancer patients. Through such preclinical researches, we have already identified candidate factors involved in irAE occurrence, and are currently planning to confirm their importance in cancer patients.
In clinical practice, there are various phenotypes of irAEs, and it is often difficult to control them. In collaboration with Kyoto University Hospital, we are working on the development of appropriate diagnosis and treatment for irAE. In advance, we have made the teams with the departments not only directly involved in the treatment of cancer but also in the diagnosis and treatment of immune mediated inflammatory diseases. In October 2021, we launched the "irAE Unit" at the Cancer Center in Kyoto University Hospital, and established a framework for members of the Department of Oncology, Department of Clinical immunology and the Department of Pharmacy to discuss how to deal with irAE.
According to the statement above, from the perspective of both basic molecular biology and medical doctors in real world practice, we would like to promote bidirectional research and realize novel application from a bench to clinic.
