Williams Cancer Institute

Unlocking the Potential of the Gut Microbiome in Cancer Treatment: A Beacon of Hope in the Fight against CRC

In the ongoing pursuit of enhancing cancer therapies, immune checkpoint blockade (ICB) therapy has emerged as a promising avenue to activate the immune system and combat tumors across various cancer types. However, its efficacy varies widely among patients and cancer types, with many exhibiting primary resistance to this treatment.

A team of researchers has embarked on a scientific journey to delve deeper into this variability in response to ICB therapy. Their journey begins with the gut microbiome, the ecosystem of microorganisms residing in our intestines, increasingly recognized for its impact on health and disease.

Through an innovative study employing animal models of colorectal cancer (CRC), researchers have pinpointed specific bacteria that bolster the effectiveness of ICB therapy. This discovery not only offers fresh insights into the interplay between the microbiome and cancer treatment response but also presents a promising pathway towards more potent therapies.

A notable finding of this study revolves around a particular strain of Bifidobacterium pseudolongum, isolated from CRC tumors treated with ICB. This commensal intestinal bacterium was found to enhance the immune response, particularly by activating a conventional dendritic cell (cDC)-dependent helper T cell 1 (TH1) circuit, resulting in a significant enhancement in the efficacy of ICB therapies in mouse models of intestinal and epithelial tumors.

In addition to identifying these ICB-boosting bacteria, the study sheds light on the underlying molecular mechanisms. Inosine, a pivotal bacterial metabolite, was found to play a crucial role by acting through A2AR-specific signaling in T cells to promote TH1 cell activation in a context-dependent manner.

The clinical relevance of these findings is underscored by the revelation that the ICB-enhancing bacteria identified in this study also exist in humans. Human fecal microbiome data revealed a trend towards enriched presence of B. pseudolongum in cancer patients who positively responded to ICB therapy, hinting at the potential for clinical translation of these findings.

However, the research journey does not culminate here. Scientists caution against blocking inosine-A2AR signaling for cancer immunotherapy, as it may nullify the beneficial effects of gut microbes. Instead, they propose that this signaling pathway could be pivotal for combined bacteria and ICB therapies.

In summary, this study not only paves the way for a deeper understanding of the microbiome-cancer therapy interaction but also offers a hopeful avenue for improving CRC and other cancer treatments. With optimism for future investigations on the effects of xanthine and hypoxanthine, as well as other facets of the microbiome, this study marks a significant stride forward in the battle against cancer.

Reference: Loeb S, Hua Q, Bauer SR, et al. (February 14, 2024). Plant-Based Diet a Boon for Men With Prostate Cancer. https://www.medscape.com/viewarticle/plant-based-diet-boon-men-prostate-cancer-2024a1000342?ecd=WNL_trdalrt_pos1_240215_etid6314473&uac=443044DR&impID=6314473

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