国际视野丨Amany Zekry教授：肠道微生物如何影响肿瘤免疫治疗的反应？

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Amany Zekry: Thank you so much. The mechanisms will be diverse, and they are still being studied. It is a very exciting area of research where we are trying to exactly dissect out the relationship between the microbiome and the response to immunotherapy. There is no doubt that we know that the microbiome can influence the response to immunotherapy, and the mechanism can be through many ways. One of them is that the microbiome can influence the immune system. It has a huge effect on the immune system, it can direct it to be a friendly immune system or an immune system that can actually be resistant to the immunotherapy. That has been shown in many studies, including studies related to immunotherapy in advanced liver cancer and melanoma. The second mechanism which also has been coupled to the immune system is the basic process whereby the microbiome can have similar epitopes to tumor neoantigen, meaning that the tumor and the microbiome can have some similar sequences which can provoke the immune response to act. That has been shown in studies related to melanoma, for instance, whereby Bifidobacterium in the microbiome was shown to share some sequences similar to melanoma, and patients who actually had a reaction to this sequence responded better to immunotherapy. This is what we call antigen mimicry of tumor neoantigen. So immune system manipulation is one mechanism. Antigen mimicry is another mechanism. The final thing is influencing the inflammatory response - whether to make the environment either pro- or anti-inflammatory, again depending on how the microbiome orchestrates this process.

Amany Zekry: I believe it is going to be very critical and a game-changer when we understand exactly how the microbiome influences the response to immunotherapy, because the microbiome is modifiable. It can change. We can change it. We can modify it. Therefore, understanding exactly this intricate and intimate relationship between the microbiome and response to immunotherapy would allow us to direct these gut-based strategies to manipulate the microbiome so we can improve patient outcomes and response to immunotherapy. It can even go beyond immunotherapy - it can prevent cancer occurrence or recurrence by a process whereby we can find the mechanism so we can engineer the changes in the gut environment to benefit our patients.

Amany Zekry: In relation to the microbiome, the research is diverse and there is a huge potential for breakthroughs and findings that will be game-changing in terms of immunotherapy for cancer. We are now trying to understand the tumors themselves. Some of the tumors are quite heterogeneous and may require different combinations of immunotherapy. The right combination will perhaps be worked out as we progress in our research. Secondly, we will also have diverse and important findings in diagnostic tests to tell us what will be the best combination of immunotherapy for cancer. Whether these diagnostic tests can be from the blood or tumor tissue or the microbiome, or from all of the above, the research is moving quite fast to give us biomarkers for diagnostic as well as prognostic purposes. Then we can tell which patients will benefit the most from immunotherapy, and which patients may not benefit and need alternative therapies to offset the cancer. The research in terms of cancer immunotherapy is progressing fast. We need biomarkers. We need to know what combination will benefit our patients. We need to know how we can manipulate the microbiome or its effects, like metabolites, to improve the response to immunotherapy. These are key aspects that the future will inform us about.