Tim F. Greten, MD, deputy chief and senior investigator of the Thoracic and Gastrointestinal Malignancies Branch at the National Cancer Institute, discusses the role of the gut microbiome in antitumor immunity in liver cancer. 

Through bile acid metabolism in the gut microbiome, specific bacteria can develop and lead to the accumulation of bile acids that control immune cells in the liver. This accumulation may influence CD4+ T cells and antitumor immunity, reports Greten. 

Preclinical data showed enough promise to begin evaluating this in a clinical trial, adds Greten. In the trial, patients will receive antibiotics that target specific bacteria in the gut. From there, antitumor immunity will be measured to see if a response is found. This treatment modality could change the landscape of liver cancer because it does not fall under the category of chemotherapy or immunotherapy, concludes Greten.

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Tim F. Greten, MD, discusses the role of the gut microbiome in antitumor immunity in liver cancer. 

Dr. Greten on the Tumor Microbiome and Antitumor Immunity in Liver Cancer

Tim F. Greten, MD, senior investigator, Thoracic and Gastrointestinal Malignancies Branch, National Cancer Institute, discusses the impact of the gut microbiome on liver tumors.

Greten and his team were interested in studying how the gut microbiome affected antitumor immunity in the liver. When the bacteria in the gut of animal models were depleted, it impaired tumor growth in multiple cases. This occurrence was then studied in more detail in order to detect the mechanism, Greten says.

The next question asked was, how can antibiotic treatment lead to fewer tumors and more natural killer T (NKT) cells in the liver? Investigators observed that giving antibiotics to mice with liver tumors resulted in an increase in the number of NKT cells. NKT cells can kill tumor cells, improving the antitumor immune response. Through this work, Greten says that the mechanism by which the bacteria metabolize and travel was discovered.

Tim F. Greten, MD, senior investigator, Thoracic and Gastrointestinal Malignancies Branch, National Cancer Institute, discusses the impact of the gut microbiome on liver tumors.
 

Dr. Greten Discusses the Impact of the Gut Microbiome on Liver Tumors

Tim F. Greten, MD, senior investigator thoracic and gastrointestinal oncology branch, head, gastrointestinal malignancy section, National Cancer Institute, discusses promising immunotherapy agents being investigated in hepatocellular carcinoma (HCC). 

The immunotherapy that is furthest developed in this space is nivolumab (Opdivo), which is being investigated in a phase III study, explains Greten. 

,br>Additionally, cell-based therapies are being looked at but they are harder to investigate as there are very little data to analyze, states Greten. 

Chimeric antigen receptor (CAR) T-cell therapy has not been very successful in solid cancers but it is 1 of the future areas that will be studied for patients with HCC. 

Tim F. Greten, MD, senior investigator thoracic and gastrointestinal oncology branch, head, gastrointestinal malignancy section, National Cancer Institute, discusses promising immunotherapy agents being investigated in hepatocellular carcinoma (HCC).

Dr. Greten on Promising Immunotherapy Agents in HCC 

Tim F. Greten, MD, senior investigator thoracic and gastrointestinal oncology branch, head, gastrointestinal malignancy section, National Cancer Institute (NCI), discusses the potential for immunotherapy in hepatocellular carcinoma (HCC).

There is a significant need for new therapies in liver cancer, as it is one of the most frequent tumors worldwide and treatments are very limited, especially for patients with advanced disease, says Greten. 

Risk factors for liver cancer include chronic viral infection and hepatitis, which both cause chronic inflation. Using an immune-based approach is fairly obvious in this scenario, says Greten. 

In recent years, there have been multiple pre-clinical studies indicating that immunotherapy may be a viable option for patients with liver cancer, and now with the increase of checkpoint inhibitors throughout oncology, more studies are being conduced in HCC, says Greten.

There is early promise with checkpoint inhibitors in this disease and patients are showing a response to an immune-based approach.

People used to think that liver cancer was the wrong disease for an immune-based approach, but liver cancer appears to be much more immunogenic than one would assume, says Greten.

Tim F. Greten, MD

Articles

Dr. Greten on the Tumor Microbiome and Antitumor Immunity in Liver Cancer

Dr. Greten Discusses the Impact of the Gut Microbiome on Liver Tumors

Dr. Greten on Promising Immunotherapy Agents in HCC

Dr. Tim F. Greten on Immunotherapy in HCC