Mechanism Identified for Potential Activation of Hidden Lymphoma During Cancer Immunotherapy (Okayama University, Ehime Prefectural Central Hospital, Kyushu University Hospital)

This is a press release regarding the collaborative research results of Okayama University, Ehime Prefectural Central Hospital, and Kyushu University Hospital.

June 15, 2026 National University Corporation Okayama University

<Key Points of the Announcement>

- Clarified the mechanism by which immune cells activated by cancer immunotherapy assist in the proliferation of hidden lymphoma.

- On the other hand, the risk is minor compared to the efficacy of cancer immunotherapy, and there is no need to be overly fearful. By understanding this risk and conducting appropriate, regular checks, safer continuation of treatment can be expected.

◆ Overview

A research group led by Professor Yosuke Togashi of the Future Medicine Creation Research Institute, which is part of the Institute for Academic and Research Assembly, Okayama University (concurrently of the Department of Respiratory Medicine, Okayama University Hospital), Guest Researcher Joji Nagasaki of Okayama University (at the time of the study; currently at Osaka Metropolitan University), Part-time Researcher Toshifumi Ninomiya (at the time of the study; currently at Kyushu University Hospital), Graduate Student Caiyang Fang (Doctoral Course, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University), and Chief of Respiratory Medicine Tomoya Katsuta of Ehime Prefectural Central Hospital, has clarified for the first time in the world that during the administration of immune checkpoint inhibitors (ICIs) such as anti-PD-1 antibodies, which are widely used in cancer treatment, there is a possibility that lymphoma, a type of blood cancer hidden in some patients, may emerge, and has uncovered part of the mechanism.

The research group analyzed a large-scale database of lung cancer patients in Japan who received ICIs and discovered that, although the frequency is very low, the risk of finding lymphoma was significantly higher compared to patients who did not receive the therapy. They clarified part of the mechanism: cells that normally act as allies of the immune system (follicular helper T cells) activated by ICIs promote the proliferation of hidden lymphoma cells. The results of this study were published in the international academic journal "Clinical Cancer Research, a journal of the American Association for Cancer Research" on May 18, 2026 (23:00 JST).

This study revealed the existence of a previously poorly recognized complication—the deterioration and manifestation of hidden lymphoma—in cancer immunotherapy, which is sometimes used over the long term, and highlighted the importance of conducting thorough, regular checkups. While the risk is extremely small compared to the efficacy of cancer immunotherapy and there is no need to be overly concerned, thorough checkups are expected to enable patients to safely continue cancer immunotherapy. This achievement will contribute significantly to further improving the safety of cancer treatments.

◆ Comment from Professor Yosuke Togashi

"Since cancer immunotherapy activates various immune cells, we, along with researchers in hematology, were interested in whether such a phenomenon could occur in cancers of blood immune cells, and it was discovered during actual clinical practice. I deeply admire the observation skills of the doctor who first noticed and informed me, and I would like to take this opportunity to express my gratitude. Nonetheless, the risk is very low compared to the benefits of general cancer immunotherapy, so I believe there is no need to be overly fearful."

◆ Publication Information Paper Title: Incidence of B cell malignancies in patients with lung cancer receiving PD-1 blockade therapy Journal: Clinical Cancer Research Authors: Toshifumi Ninomiya, Caiyang Fang, Hirofumi Hamano, Teruya Morinaga, Wenhao Zhou, Toshihiro Koyama, Sakura Miki, Li Zhu, Yusuke Naoi, Daisuke Ennishi, Tomoya Katsuta, Kadoaki Ohashi, Shin Morizane, Tomoka Ohki-Ikeda, Tatsuya Nishi, Youki Ueda, Takamasa Ishino, Yoshinobu Maeda, Isamu Okamoto, Yoshito Zamami, Joji Nagasaki, Yosuke Togashi DOI: 10.1158/1078-0432

◆ Research Funding This study was supported by the Japan Society for the Promotion of Science (JSPS): Grants-in-Aid for Scientific Research (S) JP21H05051, Grant-in-Aid for Research Activity Start-up JP22K20824, Grants-in-Aid for Early-Career Scientists JP23K14594, JP25K19576, Fostering Joint International Research JP23KK0149, Grants-in-Aid for Scientific Research (B) JP24K02459; and the Japan Agency for Medical Research and Development (AMED): Practical Research Project for Innovative Cancer Therapeutics.