Investigating the Link Between Gut Bacteria and Cancer Immunotherapy Success

Overview of Cancer Immunotherapy

In laboratory studies involving mice, researchers explored the relationship between the effectiveness of an experimental cancer immunotherapy drug and the presence of gut bacteria. Different treatment strategies are employed to tackle various forms of cancer, with cancer immunotherapy drugs designed to enhance the body’s immune system in targeting abnormal tumor cells. Some tumor cells utilize surface proteins to camouflage themselves from immune responses, and the protein CD47 is notably present on many tumor cells, sending a “don’t-eat me” signal to macrophages, the white blood cells responsible for attacking and dismantling abnormal cells.

Role of Anti-CD47 Immunotherapy

An experimental anti-CD47 cancer immunotherapy drug aims to inhibit the CD47 protein, thus enabling macrophages to effectively attack tumor cells. Initial laboratory experiments with tumor-bearing mice revealed varied responses to the anti-CD47 treatment; while some mice benefited, others did not. This discrepancy has led to an increasing recognition of the role “good” gut bacteria may play in enhancing cancer immunotherapy, potentially by stimulating gut immunity.

Research Findings from the Universities of Texas and Chicago

Researchers from the Universities of Texas Southwestern Medical Center and Chicago conducted further investigations to understand the connection between anti-CD47 immunotherapy success and gut bacteria. Their findings, published in the Journal of Experimental Medicine, focused on two groups of tumor-bearing mice with differing gut bacterial compositions. One group responded positively to anti-CD47 treatment, while the other did not. When these groups were housed together, the previously unresponsive group began to show a positive response to the treatment, suggesting a transfer of gut bacteria between the groups.

Insights on Bifidobacterium and Immune Response

Further experiments revealed that a specific type of gut bacteria, Bifidobacterium, migrates from the gut and accumulates within tumor cells. The combination of the anti-CD47 drug and Bifidobacterium was found to work synergistically through innate immune system pathways, transforming non-responsive tumors into responsive ones. Additionally, the research indicated that mice responding to anti-CD47 ceased to do so when treated with antibiotics that eliminated their gut bacteria. Conversely, anti-CD47 non-responsive mice exhibited responsiveness when supplemented with Bifidobacterium.

Implications for Future Cancer Treatments

“We felt we needed to improve anti-CD47 therapy and understand the mechanisms [of action],” stated Prof. Yang-Xin Fu, the lead investigator. “This study finds that some of the bacteria from the gut travel to the tumor and infiltrate the cells or microenvironment, where the bacteria enhance the CD47 blockade’s effectiveness against the tumor.” This process occurs through the activation of immune signaling pathways. The findings indicate that probiotics may enhance the efficacy of anti-CD47 therapy, and researchers plan to further explore whether other gut bacteria types can also influence cancer immunotherapy outcomes.

References

1. Shi Y, Zheng W, Yang K, et al. Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling. J Exp Med 2020, 217(5):e20192282. doi.org/10/1084/jem.20192282.
2. University of Texas Southwestern Medical Center. Press release, 6 Mar 2020. “Could cancer immunotherapy success depend on gut bacteria?” https://www.eurekalert.org/pub_releases/2020-03/usmc-cci030620.php
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