Will the dilemma of "immunotherapy" for liver cancer be overcome? Taipei Veterans General Hospital study: Gut microbiota profile predicts treatment response rate
Liver cancer occurs in more than 10,000 new cases every year, with 60% of patients in the late stages
The number of Taiwanese people who develop liver cancer has not declined significantly, and it is even called a “national disease.” Dr. Huang Yixiang, director of the gastroenterology and hepatobiliary department of Taipei Veterans General Hospital, said that liver cancer ranks fourth among the top ten cancers in terms of incidence, with about 10,000 new people added every year, and patients with intermediate and advanced liver cancer account for about 60%.
Current treatments for liver cancer include surgery, electrocautery, and embolization. In recent years, there have been treatments such as targeted therapy and proton heavy particles. Once liver cancer invades or metastasizes and cannot undergo surgery, embolization, or electrocautery, systemic treatment is required, among which immunotherapy is the first choice. However, immunotherapy does not have obvious effects on all liver cancer patients.
Dilemma of liver cancer immunotherapy: lack of effective biological indicators to predict efficacy
Dr. Huang Yixiang said that immunotherapy is the most important treatment method for advanced liver cancer. The effective rate of immunotherapy alone is about 15%-20%, and the effective rate of combined treatment is about 30%. However, immunotherapy for liver cancer is not like other cancers where PD-L1 can be used as an effective biomarker to predict efficacy. In liver cancer patients, regardless of the level of PD-L1 expression, a certain proportion respond to immunotherapy. It shows that there is currently a lack of effective biological indicators to predict the therapeutic effect of immunotherapy on liver cancer.
Dr. Huang Yixiang pointed out that immunotherapy for liver cancer is not covered by health insurance, and patients often have to spend high costs to receive treatment before they can know whether they are responding to immunotherapy. Therefore, finding more effective biomarkers for liver cancer immunotherapy is extremely important to help cancer patients reduce their financial burden and improve personalized treatment effects.
Is immunotherapy for liver cancer related to the intestine? Bacterial phase affects reaction rate and survival rate
Since 2018, Taipei Veterans General Hospital has collected stool samples from 41 liver cancer patients receiving immunotherapy and compared them with samples from 17 healthy subjects for next-generation gene sequencing of gastrointestinal microflora. Subsequent analysis and verification were conducted on 33 liver cancer patient specimens. Studies have found that patients with good bacteria in their intestines have significantly better liver tumor responses to immunotherapy and better survival rates.
Dr. Huang Yixiang said that more “Prevotella 9” (Bacteroidetes) was observed in the stools of patients with tumor progression; while the stools of patients who had a good response to immunotherapy were found to be “Clostridium” (Lachnoclostridium Firmicutes) and Veillonella (Firmicutes) accounted for the majority. At the same time, the abundance of Clostridium was significantly correlated with the concentration of “secondary bile acid” in the patient’s feces.
Studies have shown that liver cancer patients with better intestinal bacteria have longer survival times after receiving immunotherapy, and their risk of death is reduced by about 70%. Subsequent data on the prediction of treatment response rate through bacterial phase analysis also found that the treatment response rate of liver cancer patients with good intestinal bacterial phase can be as high as 50%. Liver cancer patients with healthy intestinal bacteria also have the longest survival period without worsening.
This study by the Taipei Veterans General Hospital team won the best research in the liver cancer category at this year’s European Society of Liver Diseases Annual Meeting, and has been published in the internationally renowned journal “Journal for ImmunoTherapy of Cancer”.
Gut and immune function are closely linked. Microflora can regulate cancer treatment response
Dr. Huang Yixiang pointed out that there are trillions of intestinal bacteria coexisting in the human intestinal system, which are closely related to the body’s nutrition, metabolism, immunity and other functions. Not only liver cancer, but also studies have shown that intestinal microflora can regulate the response of melanoma, some lung cancers and kidney cancers to immunotherapy.
Dr. Huang Yixiang said that the results of this study on intestinal bacteria and liver cancer immunotherapy will help clinicians to non-invasively predict the tumor response and survival prognosis of liver cancer patients after receiving immunotherapy, and provide patients with better information. Appropriate treatment models to combat liver cancer and reduce liver cancer mortality.
Dr. Huang Yixiang pointed out that there are currently no probiotic products related to “Clostridium trichophyton” on the market. However, there is a positive correlation between Clostridium pilosum and secondary bile acid, and there is an opportunity to conduct research on predicting the effectiveness of immunotherapy based on differences in bile acid concentration. At the same time, research on microflora transplantation therapy has emerged in recent years. It is expected to collect fecal samples from “super donors” to conduct research on the improvement of intestinal flora and the treatment of liver cancer through microflora implantation.
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