biostudies-literatureBender MJNIDDK NIH HHSNIAID NIH HHSNCI NIH HHSNIGMS NIH HHSNIH HHS1846-1862.e26https://www.ebi.ac.uk/biostudies/studies/S-EPMC10148916biostudies-literatureUnknown186(9)The use of probiotics by cancer patients is increasing, including among those undergoing immune checkpoint inhibitor (ICI) treatment. Here, we elucidate a critical microbial-host crosstalk between probiotic-released aryl hydrocarbon receptor (AhR) agonist indole-3-aldehyde (I3A) and CD8 T cells within the tumor microenvironment that potently enhances antitumor immunity and facilitates ICI in preclinical melanoma. Our study reveals that probiotic Lactobacillus reuteri (Lr) translocates to, colonizes, and persists within melanoma, where via its released dietary tryptophan catabolite I3A, it locally promotes interferon-γ-producing CD8 T cells, thereby bolstering ICI. Moreover, Lr-secreted I3A was both necessary and sufficient to drive antitumor immunity, and loss of AhR signaling within CD8 TCellDietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment.PMC10148916U01 CA272541P01 AI108545R01 CA253329F32 CA247004R21 AI163721P50 CA254865P20 GM103418R01 DK129950U01 CA268806P30 CA047904T32 CA082084R01 DK130897R56 AI168478R21 CA259636R01 CA203689T32 AI089443R01 CA222203S10 OD023402McCulloch JACervantes-Barragan LGelhaus SLRichie TGLee STMGocher-Demske AMMedina Sanchez LZarour HMPierre JFPhelps CMDavar DMullett SJRana MLaughlin CRMims TSMcPherson ACShapira JHBender MJJoglekar AVCannon NHinterleitner RPandey SPVignali DAABruno TCMeisel MfalseDietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment.The use of probiotics by cancer patients is increasing, including among those undergoing immune checkpoint inhibitor (ICI) treatment. Here, we elucidate a critical microbial-host crosstalk between probiotic-released aryl hydrocarbon receptor (AhR) agonist indole-3-aldehyde (I3A) and CD8 T cells within the tumor microenvironment that potently enhances antitumor immunity and facilitates ICI in preclinical melanoma. Our study reveals that probiotic Lactobacillus reuteri (Lr) translocates to, colonizes, and persists within melanoma, where via its released dietary tryptophan catabolite I3A, it locally promotes interferon-γ-producing CD8 T cells, thereby bolstering ICI. Moreover, Lr-secreted I3A was both necessary and sufficient to drive antitumor immunity, and loss of AhR signaling within CD8 T2023-01-01T00:00:00Z2023 Apr2026-06-02T08:40:02.926Z2026-05-25T03:06:58.003ZS-EPMC101489163702842810.1016/j.cell.2023.03.011