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BACKGROUND: Gut bacteria are related to immune checkpoint inhibitors (ICIs). However, there is inconsistency in ICI-associated species, while the role of non-bacterial microbes in immunotherapy remains elusive. Here, we evaluated the association of trans-kingdom microbes with ICIs by multi-cohort multi-cancer analyses. METHODS: We retrieved fecal metagenomes from 1,359 ICI recipients with four different cancers (metastatic melanoma MM, non-small cell lung carcinoma NSCLC, renal cell cancer RCC, and hepatocellular carcinoma) from 12 published datasets. Microbiota composition was analyzed using the Wilcoxon rank test. The performance of microbial biomarkers in predicting ICI response was assessed by random forest. Key responder-associated microbes were functionally examined in vitro and in mice. FINDINGS: T cell activity in vitro and in mice. Moreover, bacterial and eukaryotic biomarkers showed great performance in predicting ICI response in patients from discovery and two validation cohorts (MM: area under the receiver operating characteristic curve AUROC = 72.27%-80.19%; NSCLC: AUROC = 72.70%-87.98%; RCC: AUROC = 83.33%-89.58%). CONCLUSIONS: This study identified trans-kingdom microbial signatures associated with ICI in multi-cancer and specific cancer types. Trans-kingdom microbial biomarkers are potential predictors of ICI response in patients with cancer. FUNDING: Funding information is shown in the acknowledgments.
Lin et al. (Thu,) studied this question.