Overcoming immunotherapy resistance and inducing abscopal effects with boron neutron immunotherapy (B-NIT).

Autor: Fujimoto T; Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.; Neutron Therapy Research Center, Okayama University, Okayama, Japan., Yamasaki O; Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.; Department of Dermatology, Shimane University Faculty of Medicine, Izumo, Japan., Kanehira N; Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.; Neutron Therapy Research Center, Okayama University, Okayama, Japan., Matsushita H; Division of Translational Oncoimmunology, Aichi Cancer Center Research Institute, Nagoya, Japan., Sakurai Y; Institute for Integrated Radiation and Nuclear Science, Kyoto University, Sennan-gun, Japan., Kenmotsu N; Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.; Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan., Mizuta R; Division of Translational Oncoimmunology, Aichi Cancer Center Research Institute, Nagoya, Japan.; Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan., Kondo N; Institute for Integrated Radiation and Nuclear Science, Kyoto University, Sennan-gun, Japan., Takata T; Institute for Integrated Radiation and Nuclear Science, Kyoto University, Sennan-gun, Japan., Kitamatsu M; Faculty of Science and Engineering, Kindai University, Higashiosaka, Japan., Igawa K; Neutron Therapy Research Center, Okayama University, Okayama, Japan., Fujimura A; Neutron Therapy Research Center, Okayama University, Okayama, Japan.; Department of Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan., Otani Y; Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan., Shirakawa M; Neutron Therapy Research Center, Okayama University, Okayama, Japan., Shigeyasu K; Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan., Teraishi F; Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan., Togashi Y; Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan., Suzuki M; Institute for Integrated Radiation and Nuclear Science, Kyoto University, Sennan-gun, Japan., Fujiwara T; Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan., Michiue H; Neutron Therapy Research Center, Okayama University, Okayama, Japan.
Jazyk: angličtina
Zdroj: Cancer science [Cancer Sci] 2024 Oct; Vol. 115 (10), pp. 3231-3247. Date of Electronic Publication: 2024 Aug 09.
DOI: 10.1111/cas.16298
Abstrakt: Immune checkpoint inhibitors (ICIs) are effective against many advanced malignancies. However, many patients are nonresponders to immunotherapy, and overcoming this resistance to treatment is important. Boron neutron capture therapy (BNCT) is a local chemoradiation therapy with the combination of boron drugs that accumulate selectively in cancer and the neutron irradiation of the cancer site. Here, we report the first boron neutron immunotherapy (B-NIT), combining BNCT and ICI immunotherapy, which was performed on a radioresistant and immunotherapy-resistant advanced-stage B16F10 melanoma mouse model. The BNCT group showed localized tumor suppression, but the anti-PD-1 antibody immunotherapy group did not show tumor suppression. Only the B-NIT group showed strong tumor growth inhibition at both BNCT-treated and shielded distant sites. Intratumoral CD8+ T-cell infiltration and serum high mobility group box 1 (HMGB1) levels were higher in the B-NIT group. Analysis of CD8 + T cells in tumor-infiltrating lymphocytes (TILs) showed that CD62L- CD44 + effector memory T cells and CD69 + early-activated T cells were predominantly increased in the B-NIT group. Administration of CD8-depleting mAb to the B-NIT group completely suppressed the augmented therapeutic effects. This indicated that B-NIT has a potent immune-induced abscopal effect, directly destroying tumors with BNCT, inducing antigen-spreading effects, and protecting normal tissue. B-NIT, immunotherapy combined with BNCT, is the first treatment to overcome immunotherapy resistance in malignant melanoma. In the future, as its therapeutic efficacy is demonstrated not only in melanoma but also in other immunotherapy-resistant malignancies, B-NIT can become a new treatment candidate for advanced-stage cancers.
(© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
Databáze: MEDLINE
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