biostudies-literatureDi Luccia BNCATS NIH HHSNIDDK NIH HHSCrohn's & Colitis FoundationNCI NIH HHSeadi5374https://www.ebi.ac.uk/biostudies/studies/S-EPMC11299520biostudies-literatureUnknown9(95)The gut microbiota and tumor-associated macrophages (TAMs) affect tumor responses to anti-programmed cell death protein 1 (PD-1) immune checkpoint blockade. Reprogramming TAM by either blocking or deleting the macrophage receptor triggering receptor on myeloid cells 2 (TREM2) attenuates tumor growth, and lack of functional TREM2 enhances tumor elimination by anti-PD-1. Here, we found that anti-PD-1 treatment combined with TREM2 deficiency in mice induces proinflammatory programs in intestinal macrophages and a concomitant expansion of <i>Ruminococcus gnavus</i> in the gut microbiota. Gavage of wild-type mice with <i>R. gnavus</i> enhanced anti-PD-1-mediated tumor elimination, recapitulating the effect occurring in the absence of TREM2. A proinflammatory intestinal environment coincided witScience immunologyTREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti-PD-1 tumor immunotherapy.PMC11299520P30 CA091842R01 CA262684R00 DK118110UL1 TR002345R01 DK119147938100P30 DK056341Chang HWTrsan TOnufer EJMolgora MColonna MCzepielewski RSda Silva CSDi Luccia BHelmink BAGilfillan SGordon JIFachi JLHou JJaeger NCella MKhantakova DBando JKBhattarai BSchreiber RDRodrigues PFfalseTREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti-PD-1 tumor immunotherapy.The gut microbiota and tumor-associated macrophages (TAMs) affect tumor responses to anti-programmed cell death protein 1 (PD-1) immune checkpoint blockade. Reprogramming TAM by either blocking or deleting the macrophage receptor triggering receptor on myeloid cells 2 (TREM2) attenuates tumor growth, and lack of functional TREM2 enhances tumor elimination by anti-PD-1. Here, we found that anti-PD-1 treatment combined with TREM2 deficiency in mice induces proinflammatory programs in intestinal macrophages and a concomitant expansion of <i>Ruminococcus gnavus</i> in the gut microbiota. Gavage of wild-type mice with <i>R. gnavus</i> enhanced anti-PD-1-mediated tumor elimination, recapitulating the effect occurring in the absence of TREM2. A proinflammatory intestinal environment coincided wit2024-01-01T00:00:00Z2024 May2026-06-01T07:17:30.591Z2025-04-06T22:44:24.443ZS-EPMC112995203875880810.1126/sciimmunol.adi5374