Fecal microbiota transplantation promotes immunotherapy sensitivity in refractory gastrointestinal cancer patients

The discovery and therapeutic application of immune checkpoint inhibitors (ICI) has significantly improved clinical outcomes in cancer treatment. However, the response rate is still low in gastrointestinal (GI) cancers. Considering the paramount role of gut microbiome in immune modulation, we performed fecal microbiota transplantation (FMT) from healthy donors in 10 GI cancer patients resistant to anti-PD-(L)1 treatment. The combination of FMT and anti-PD1 treatment was well tolerated with no serious adverse reactions observed, and 2 patients restored clinical responsiveness to anti-PD1. Clinical benefits were associated with colonization of donor-derived immunogenic microbes, and an activated immune status reflected by peripheral immune cell populations. Moreover, microbial signatures were identified for ICI responsiveness and validated in an independent cohort and in mouse model. The current study demonstrates the feasibility of FMT for ICI-refractory GI cancer patients and provides a foundation for LBP development to enhance ICI efficacy.