Specific Associate Professor Tsukamoto Hirotake, Kosaku Murakami
Not all cancer patients respond well to immunotherapy, including anti-PD-(L)1 therapy. Additionally, immune-related adverse events (irAEs) associated with immunotherapy can lead to severe organ damages and, in some cases, may be life-threatening, and thereby forcing to be discontinued. Our division is focusing on the mechanisms why some patients do not respond to immunotherapy and why others experience autoimmune reactions. By investigating these mechanisms, we aim to clarify the underlying causes of these reactions and contribute to improving the safety and efficacy of cancer immunotherapy for the patients.
Research and Education
Cancer immunotherapies, such as immune checkpoint blockade, have revolutionized cancer treatment, but many problems remain to be solved for its further improvement and widespread use. Our division, Clinical Immunology in Cancer Immunotherapy focuses on the molecular mechanisms underlying the immune-related adverse events (irAEs) and translating this knowledge into clinical practice. Excessive immunosuppression to control the irAEs has concern to decline the effectiveness of cancer immunotherapy, while boosting therapeutic efficacy increases the risk of autoimmune response. Therefore, developing strategies to balance such seemingly conflicting issues is crucial. We aim to identify key factors involved in irAE pathogenesis and establish the basis of combined cancer immunotherapies that maximize antitumor effects while minimizing irAEs. To meet clinical needs, we collaborate with Kyoto University Hospital and work with diverse divisions to create a system that supports safety in clinical care. In 2021, we established an “irAE Unit” to support patient care while investigating the causes of irAEs through the analysis of clinical data and patient samples from both basic research and clinical perspective.
Aiming to optimize the balance between anti-tumor immune response and irAEs
Laboratory members
Recet Publications
- Yokoi, M., Yonezawa, A., Hira, D., Handa, T., Tanizawa, K., Nakagawa, S., Tsuda, M., Ikemi, Y., Itotani, R., Yoshida, H., Nomura, M., Matsubara, J., Murakami, K., Ozasa, H., Muto, M., & Terada, T. (2024). Subjective symptoms are triggers for the detection of immune checkpoint inhibitor-induced interstitial lung disease and associate with disease severity: a single-center retrospective study. J Pharm Health Care Sci,10, 52, 2024.
- Miura Y., Motoshima T., Anami T., Yano H., Mito R., Pan C., Urakami S., Kinowaki K., Tsukamoto H., Kurahashi R., Murakami Y., Yatsuda J., Fujiwara Y., Kamba T., and Komohara Y. Predictive value of CXCL10 for the occurrence of immune-related adverse events in patient with renal cell carcinoma. Microbiol. Immunol. 67, 345-354, 2023.
- Tsukamoto H.*, Komohara Y., Tomita Y., Miura Y., Motoshima T., Imamura K., Kimura T., Ikeda T., Fujiwara Y., Yano H., Kamba T., Sakagami T., Oshiumi H. Aging-associated and CD4 T cell-dependent ectopic CXCL13 activation predisposes to anti-PD-1 therapy-induced adverse events. Proc. Natl. Acad. Sci. U S A. 119, e2205378119, 2022. (*corresponding author)
- Tsukamoto H.*, Kouwaki T. and Oshiumi H. Aging-associated extracellular vesicles contain immune regulatory microRNAs alleviating hyperinflammatory state and immune dysfunction in the elderly. iScience 23, 101520, 2020. (*corresponding author)
Laboratory
Tsukamoto Hirotake, Specific Associate Professor
Kosaku Murakami, Specific Associate Professor