Dual near‐infrared II laser modulates the cellular redox state of T cells and augments the efficacy of cancer immunotherapy

• DOI: 10.1096/fj.202200033r
• Publication Date: 2022-09-02T09:14:56Z
• Authors: Wataru Katagiri; Shinya Yokomizo; Takanobu Ishizuka; Keiko Yamashita; Timo Kopp; Malte Roessing; Akiko Sato; Taizo Iwasaki; Hideki Sato; Takeshi Fukuda; Hailey Monaco; Sophia Manganiello; Shinsuke Nomura; Mei Rosa Ng; Susanne Feil; Emiyu Ogawa; Dai Fukumura; Dmitriy N. Atochin; Hak Soo Choi; Satoshi Kashiwagi
• Keywords: 0301 basic medicine; Mice; 03 medical and health sciences; Lasers; Neoplasms; Animals; Immunotherapy; CD8-Positive T-Lymphocytes; Oxidation-Reduction; 3. Good health

Immunotherapy, including immune checkpoint inhibitors, has revolutionized cancer treatment, but only a minor fraction of patients shows durable responses. A new approach to overcome this limitation is yet to be identified. Recently, we have shown that photobiomodulation (PBM) with near-infrared (NIR) light in the NIR-II window reduces oxidative stress and supports the proliferation of CD8+ T cells, suggesting that PBM with NIR-II light could augment anti-cancer immunity. Here, we report a novel approach to support tumor-infiltrating CD8+ T cells upon PBM with NIR-II laser with high tissue penetration depth. Brief treatments of a murine model of breast cancer with dual 1064 and 1270 nm lasers reduced the expression of the programmed cell death protein 1 (PD-1) in CD8+ T cells in a syngeneic mouse model of breast cancer. The direct effect of the NIR-II laser treatment on T cells was confirmed by the enhanced tumor growth delay by the adoptive transfer of laser-treated CD8+ T cells ex vivo against a model tumor antigen. We further demonstrated that specific NIR-II laser parameters augmented the effect of the immune checkpoint inhibitor on tumor growth. PBM with NIR-II light augments the efficacy of cancer immunotherapy by supporting CD8+ T cells. Unlike the current immunotherapy with risks of undesirable drug-drug interactions and severe adverse events, the laser is safe and low-cost. It can be broadly combined with other therapy without modification to achieve clinical significance. In addition, our study established a path to develop a novel laser-based therapy to treat cancer effectively.