There is growing interest among cancer patients in using probiotics to improve their health, but it is still unclear how gut microbes alter cancer immunotherapy responses. A new study led by University of Pittsburgh researchers and recently Published in Cell has shown that, in mouse models, the probiotic bacterium, or “good” bacterium, Lactobacillus reuteri travels to melanoma tumors, where it promotes antitumor immunity and facilitates cancer immunotherapy by releasing indole-3-aldehyde (I3A).
They also found that advanced melanoma patients who responded to immunotherapy had higher I3A levels compared to non-responsive patients.
More studies are required, but the researchers hope that these findings will pave the way for dietary- and probiotics-based cancer therapy.
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 T cells abrogated Lr’s antitumor effects. Further, a tryptophan-enriched diet potentiated both Lr– and ICI-induced antitumor immunity, dependent on CD8 T cell AhR signaling. Finally, we provide evidence for a potential role of I3A in promoting ICI efficacy and survival in advanced melanoma patients.