A specific enterotype derived from gut microbiome of older individuals enables favorable responses to immune checkpoint blockade therapy
Cell Host Microbe. 2024 Mar 18:S1931-3128(24)00075-1. doi: 10.1016/j.chom.2024.03.002. Online ahead of print.ABSTRACTImmunotherapy has revolutionized cancer treatment, but inconsistent responses persist. Our study delves into the intriguing phenomenon of enhanced immunotherapy sensitivity in older individuals with cancers. Through a meta-analysis encompassing 25 small-to-mid-sized trials of immune checkpoint blockade (ICB), we demonstrate that older individuals exhibit heightened responsiveness to ICB therapy. To understand the underlying mechanism, we reanalyze single-cell RNA sequencing (scRNA-seq) data from multiple studies and unveil distinct upregulation of exhausted and cytotoxic T cell markers within the tumor microenvironment (TME) of older patients. Recognizing the potential role of gut microbiota in modulating the efficacy of immunotherapy, we identify an aging-enriched enterotype linked to improved immunotherapy outcomes in older patients. Fecal microbiota transplantation experiments in mice confirm the therapeutic potential of the aging-enriched enterotype, enhancing treatment sensitivity and reshaping the TME. Our discoveries confront the prevailing paradox and provide encouraging paths for tailoring cancer immunotherapy strategies according to an individual's gut microbiome profile.PMID:38513657 | DOI:10.1016/j.chom.2024.03.002
Source: Cell Host and Microbe - Category: Microbiology Authors: Xiaoqiang Zhu Xiaowen Huang Muni Hu Rongrong Sun Jiantao Li Hai Wang Xuefeng Pan Yanru Ma Lijun Ning Tianying Tong Yilu Zhou Jinmei Ding Ying Zhao Baoqin Xuan Jing-Yuan Fang Jie Hong Jason Wing Hon Wong Youwei Zhang Haoyan Chen Source Type: research