Elucidating immunotherapy resistance factors in lung cancer through world's first cellular microenvironment analysis - Expectation for new treatment development for intractable lung cancer targeting resistance factors [Kindai University, Kyoto Prefectural University of Medicine, Okayama University]

This is a joint research press release from Kindai University, Kyoto Prefectural University of Medicine, and Okayama University.

June 14, 2026 Okayama University

<Key Points> - Established a method to comprehensively analyze the "tumor microenvironment" surrounding cancer cells, and discovered indicators to accurately predict the effect of immune checkpoint inhibitors, which are cancer therapeutic drugs. - Identified resistance factors for immune checkpoint inhibitors present in immune cells and cancer cells. - This research is expected to lead to accurate prediction of immune checkpoint inhibitor efficacy and the development of combination therapies to enhance drug effectiveness.

◆ Summary A research group led by Assistant Professor Kosuke Isomoto and Assistant Professor Koji Haratani (at the time of the research) of the Department of Internal Medicine (Medical Oncology Division) at Kindai University Faculty of Medicine; Associate Professor Takahiro Tsujikawa of the Department of Otolaryngology-Head and Neck Surgery at Kyoto Prefectural University of Medicine Graduate School of Medical Science; and Professor Shuta Tomida of the Center for Comprehensive Genomic Medicine (Okayama University Hospital), Medical Development Area, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, has established an advanced method to comprehensively analyze the "tumor microenvironment" surrounding cancer cells to clarify the differences between patients for whom "immune checkpoint inhibitors," a breakthrough cancer treatment, are effective and those for whom they are not. Using this method, they successfully identified indicators that can accurately predict the response of lung cancer patients to immune checkpoint inhibitors, as well as factors that confer resistance to the drugs.

These findings are expected to enable accurate prediction of immune checkpoint inhibitor efficacy and lead to the development of new treatments that target resistance factors directly to boost drug efficacy.

The paper detailing these findings was published on May 15, 2026, in the Journal of Clinical Investigation, an international medical journal published by the American Society for Clinical Investigation. This information was officially released on May 20, 2026.

◆ Publication Information Journal: Journal of Clinical Investigation (Impact Factor: 13.6 @ 2024) Paper Title: Spatial single-cell proteotyping reveals immunotherapy-resistant features within the complex tumor microenvironment of metastatic NSCLC Authors: Kosuke Isomoto1, Koji Haratani1,2*, Takahiro Tsujikawa3, Shuta Tomida4, Yusuke Makuya5, Masayuki Takeda1, Hidetoshi Yonesaka1, Kaoru Tanaka1, Tsutomu Iwasa1, Kazuko Sakai6, Kazuto Nishio6, Akihiko Ito7, Kazuhiko Nakagawa1, Hidetoshi Hayashi1 (*Corresponding author) Affiliations: 1 Department of Internal Medicine (Medical Oncology Division), Kindai University Faculty of Medicine; 2 Dana-Farber Cancer Institute (Medical Oncology); 3 Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine Graduate School of Medical Science; 4 Center for Comprehensive Genomic Medicine (Okayama University Hospital), Medical Development Area, Okayama University Graduate School; 5 Department of Surgery (Lower Gastrointestinal Division), Kindai University Faculty of Medicine; 6 Department of Genome Biology, Kindai University Faculty of Medicine; 7 Department of Pathology, Kindai University Faculty of Medicine. URL: https://doi.org/10.1172/JCI195021 DOI: 10.1172/JCI195021

◆ Researcher's Comment Kosuke Isomoto Affiliation: Department of Internal Medicine (Medical Oncology Division), Kindai University Faculty of Medicine Position: Assistant Professor Degree: Ph.D. (Medicine) Comment: "Although it has long been suggested that the immune microenvironment within a tumor is deeply involved in the therapeutic response to immune checkpoint inhibitors, our study succeeded in demonstrating a part of its complex overall picture through detailed analysis using multiplex immunostaining. Although many steps are still required for clinical application, I hope this knowledge will contribute to a deeper understanding of the tumor microenvironment and the development of immunotherapy."

◆ For Detailed Research Content Elucidating immunotherapy resistance factors in lung cancer through world's first cellular microenvironment analysis - Expectation for new treatment development for intractable lung cancer targeting resistance factors https://www.okayama-u.ac.jp/up_load_files/press_r8/press20260520-1.pdf

◆ Inquiries Kindai University Faculty of Medicine, School of Nursing, and Hospital Operations General Affairs and Public Relations Division (Attn: Morii, Hashimoto) TEL: 072-288-7222 FAX: 072-298-1500 Kyoto Prefectural University of Medicine General Affairs Department Planning Division