Hirasawa Yuya, Isobe Junya, Hosonuma Masahiro, Tsurui Toshiaki, Baba Yuta, Funayama Eiji, Tajima Kohei, Murayama Masakazu, Narikawa Yoichiro, Toyoda Hitoshi, Shida Midori, Sasaki Aya, Maruyama Yuuki, Amari Yasunobu, Mura Emiko, Suzuki Risako, Iriguchi Nana, Ishiguro Tomoyuki, Ohkuma Ryotaro, Shimokawa Masahiro, Ariizumi Hirotsugu, Kubota Yutaro, Horiike Atsushi, Sambe Takehiko, Uchida Naoki, Wada Satoshi, Kobayashi Shinichi, Kiuchi Yuji, Kuramasu Atsuo, Yoshimura Kiyoshi, Tsunoda Takuya
Division of Medical Oncology, Department of Medicine, Showa Medical University School of Medicine, Tokyo, Japan.
Department of Hospital Pharmaceutics, School of Pharmacy, Showa Medical University, Tokyo, Japan.
Front Immunol. 2025 May 22;16:1528521. doi: 10.3389/fimmu.2025.1528521. eCollection 2025.
The rapid increase in the number of elderly patients with cancer necessitates treatment strategies based on the effects of aging because of drastic side effects of cytotoxic anticancer agents. Immune checkpoint inhibitors (ICIs) are relatively less toxic and can be easily administered to vulnerable and aged patients suffering from cancer. The diversity of gut microbiota and specific bacteria affects the efficacy and safety of ICIs. Therefore, this study aimed to assess the effect of aging on gut microbiota that play crucial roles in determining antitumor efficacy of drugs.
Stool samples were collected from 36 aged patients pathologically diagnosed with solid tumors before the start of drug therapy, and gut microbial composition was analyzed using next generation sequencing. The association between gut microbiota and efficacy and safety of ICIs was analyzed.
The abundance of species significantly decreased in patients aged ≥75 years. Additionally, the gut microbiota in the responder group was significantly higher than that in the non-responder group regardless of age. The abundance of species was significantly higher in the responder group than that in the non-responder group.
These gut microbiota changes with aging, and its characteristics are important parameters that also affect the efficacy of ICIs.
由于细胞毒性抗癌药物的严重副作用，老年癌症患者数量的迅速增加使得基于衰老影响的治疗策略成为必要。免疫检查点抑制剂（ICIs）毒性相对较小，可轻松用于患有癌症的脆弱老年患者。肠道微生物群的多样性和特定细菌会影响ICIs的疗效和安全性。因此，本研究旨在评估衰老对在决定药物抗肿瘤疗效中起关键作用的肠道微生物群的影响。
在药物治疗开始前，从36例经病理诊断患有实体瘤的老年患者中采集粪便样本，并使用下一代测序技术分析肠道微生物组成。分析肠道微生物群与ICIs疗效和安全性之间的关联。
≥75岁患者中某物种的丰度显著降低。此外，无论年龄如何，应答组的肠道微生物群均显著高于无应答组。应答组中某物种的丰度显著高于无应答组。
这些肠道微生物群随衰老而变化，其特征是影响ICIs疗效的重要参数。
