| Autor: |
Yujiro Naito, Shohei Koyama, Kentaro Masuhiro, Takashi Hirai, Takeshi Uenami, Takako Inoue, Akio Osa, Hirotomo Machiyama, Go Watanabe, Nicolas Sax, Jordan Villa, Yumi Kinugasa-Katayama, Satoshi Nojima, Moto Yaga, Yuki Hosono, Daisuke Okuzaki, Shingo Satoh, Takeshi Tsuda, Yoshimitsu Nakanishi, Yasuhiko Suga, Takayoshi Morita, Kiyoharu Fukushima, Masayuki Nishide, Takayuki Shiroyama, Kotaro Miyake, Kota Iwahori, Haruhiko Hirata, Izumi Nagatomo, Yukihiro Yano, Motohiro Tamiya, Toru Kumagai, Norihiko Takemoto, Hidenori Inohara, Sho Yamasaki, Kazuo Yamashita, Taiki Aoshi, Esra A. Akbay, Naoki Hosen, Yasushi Shintani, Hyota Takamatsu, Masahide Mori, Yoshito Takeda, Atsushi Kumanogoh |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Science Advances. 9 |
| ISSN: |
2375-2548 |
| DOI: |
10.1126/sciadv.ade0718 |
| Popis: |
Immune checkpoint inhibitors (ICIs) have caused revolutionary changes in cancer treatment, but low response rates remain a challenge. Semaphorin 4A (Sema4A) modulates the immune system through multiple mechanisms in mice, although the role of human Sema4A in the tumor microenvironment remains unclear. This study demonstrates that histologically Sema4A-positive non–small cell lung cancer (NSCLC) responded significantly better to anti–programmed cell death 1 (PD-1) antibody than Sema4A-negative NSCLC. Intriguingly, SEMA4A expression in human NSCLC was mainly derived from tumor cells and was associated with T cell activation. Sema4A promoted cytotoxicity and proliferation of tumor-specific CD8 + T cells without terminal exhaustion by enhancing mammalian target of rapamycin complex 1 and polyamine synthesis, which led to improved efficacy of PD-1 inhibitors in murine models. Improved T cell activation by recombinant Sema4A was also confirmed using isolated tumor-infiltrating T cells from patients with cancer. Thus, Sema4A might be a promising therapeutic target and biomarker for predicting and promoting ICI efficacy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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