APASL2023 Interview | Professor Tim Greten: Research status, application and challenges of biomarkers related to immunotherapy of liver cancer

Editor's note: As a new treatment method, tumor immunotherapy has changed the clinical treatment mode of liver cancer, and gradually developed into a new type of anti-tumor drugs after molecular targeted drugs. The continuous emergence of various types of immune checkpoint inhibitors has also brought new hope to the majority of liver cancer patients. However, in reality, the response rate of immunotherapy is limited. Looking for accurate tumor immunotherapy biomarkers as targets or detection and evaluation indicators can help to get rid of this dilemma, and exploring more effective immunotherapy models can benefit patients more. With the deepening of research, immunotherapy will bring more dawn to cancer patients. At the 32nd Asia-Pacific Association for Liver Research (APASL) annual meeting, this journal had the honor to interview Professor Tim Greten of the National Cancer Research Center of the National Institutes of Health of the United States, sharing the research status, application and challenges of biomarkers related to immunotherapy of liver cancer.

IH: In recent years, which immune-related biomarkers have been found for the systemic  therapy of HCC?

Prof. Greten: As you probably know, immune checkpoint inhibitors have shown significant advances in HCC, and have now become standard-of-care treatment. Unfortunately, not all patients benefit from this treatment. There have been various approaches to identify biomarkers. There are mainly three different types - immunohistochemistry with PD-L1 staining, looking for tumor mutation burden, and interferon-gamma signatures. Unfortunately, none of those have really proven to be reliable biomarkers, so we are still pretty much sitting in the dark.

IH: What are the main functions of immune-related biomarkers in the systemic therapy of HCC ?

Prof. Greten: As I’ve said, we still need to find these biomarkers in order to get more precise data. We need to identify biomarkers in the future, but at the moment we can’t use what we have to predict response or choose a potential treatment.

IH: As far as you know, which biomarkers can effectively predict the efficacy of systemic therapy of HCC?

Prof. Greten: There have been attempts to do this using PD-L1 staining. As it turns out, right now we don’t have a very good biomarker.

IH: What are the main challenges we face in the research and application of immune related biomarkers in the systematic therapy of HCC? How do you see the prospect of systematic therapy of HCC in the future?

Prof. Greten: With regard to the first question related to biomarkers, I think we have to remember that a lot of the time, HCC is often diagnosed without a biopsy, which makes it difficult as we don’t have enough of a tissue archive to identify biomarkers from archived tissue. We need to put greater effort into collecting specimens. I think another very interesting approach is to study peripheral blood and circulating tumor DNA. That may help us in the future to identify biomarkers. We have to perform more thorough analyses and use more bioinformatics to identify new combinations of biomarkers. In regard to the question of future treatments, I think it is pretty obvious right now that combination immunotherapy has become standard-of-care in the first-line setting, and I am looking forward to more novel combinations. I think another interesting approach is the potential use.