編者按
第74屆美國肝病研究學會年會（AASLD 2023）剛剛於美國波士頓閉幕。四大前沿講座之一——「Leon Schiff State of the Art: Personalized Approach to HCC」上，美國妙佑醫療國際（Mayo Clinic）胃腸肝病部Lewis R. Roberts 教授不僅介紹了肝細胞癌（HCC）精準治療的原則，而且重點分享了如何從腫瘤免疫微環境視角考慮個體化治療。【國際肝病】記者有幸邀請到Lewis R. Roberts 教授，簡要分享腫瘤微環境對HCC發生和發展的影響、聯合治療的主要作用機制，以及如何為每位患者提供最佳治療。訪談影片和中英文對照訪談原稿整理如下。
腫瘤微環境影響HCC發生和發展的機制
【國際肝病】
肝癌的免疫微環境如何影響精準治療的效果？
Lewis R. Roberts教授： 作為對腫瘤發生和發展的反應，形成了腫瘤微環境，腫瘤為了不斷進展，必須能夠逃避傾向於消除腫瘤的自然免疫應答，因此，腫瘤微環境中的多種元素，包括血管的變化以及我們稱之為免疫檢查點的變化，試圖抑制免疫反應，這些分子會形成癌細胞的屏障，阻止免疫細胞攻擊它們。
英文原文
<Hepatology Digest>: How does the tumor immune microenvironment affect the efficacy of precision HCC therapy?
Dr. Lewis Roberts: Yeah. The tumor micro environments is organized in response to the growth and development of tumors and in order to the tumors to develop they have to be able to escape from the natural immune response which will tend to eliminate the tumors. And so the multiple elements within the tumor micro environment that try to suppress the immune response and they include changes in the vasculature as well as changes in what we call immune checkpoints. So these are molecules that will create a shield aligned cancer cells and prevent the immune cells from attacking them.
HCC聯合治療的主要機制及策略
【國際肝病】
聯合治療在改善肝癌腫瘤反應方面的具體效果如何，以及如何確定最佳的治療組合和時機？
Lewis R. Roberts教授： 特別是在HCC中，已經非常明確，例如貝伐珠單抗等抑制VEGF受體的藥物，透過調節VEGF受體通路，實際上是對抗腫瘤的抗免疫效應，它們不僅阻斷了腫瘤的血管生成，還阻斷了透過VEGF介導的免疫應答抑制。因此，我們可以使用這些藥物，並且與例如PD-1和PDL-1抑制劑等更多的標準免疫檢查點抑制劑聯合套用，進一步阻斷腫瘤的抑制作用。
英文原文
<Hepatology Digest>: What is the specific efficacy of combination therapies in improving tumor response in HCC, and how can the optimal treatment combinations and timing be determined?
Dr. Lewis Roberts: Specifically in HCC it is become clear that agents that inhibit the VEGF receptor such as bevacizumab actually inhibit anti tumor anti immune effects that are regulated to the VEGF receptor pathway. So they not only block angiogenesis but they also blocked the inhibition of the immune response that was mediated through the VEGF. And so we are able to use these agents then in combination with more standard immune checkpoint inhibitors such as PD1 and PDL 1 inhibitors to further block anti tumor inhibitor.
對HCC治療前景的期待
【國際肝病】
免疫治療在HCC患者的預後中起著越來越重要的作用。您如何看待這一趨勢，並如何將其套用於改善患者的治療結果？
Lewis R. Roberts教授： 隨著我們對HCC的腫瘤微環境，尤其是免疫微環境的深入了解，我們期望確定HCC其他重要的檢查點，從而可以開發藥物或聯合治療，包括針對這些其他檢查點的治療藥物。我們也在嘗試其他方法，比如套用放射療法，使腫瘤的新抗原顯露出來，期望顯露出來的新抗原也會刺激抗腫瘤的免疫反應。
英文原文
<Hepatology Digest>: Immune-based therapies are playing an increasingly important role on HCC patient outcomes. How do you see this trend evolving, and how can it be leveraged to improve patient outcomes?
Dr. Lewis Roberts: As we better understand the tumor micro environment, particularly the immune micro environment, in responses to tumor micro environment in HCC. Anticipation is that we will identify other checkpoints that are important in HCC tumors so that we can develop agents or combinations that include agents against those additional checkpoints as well. There are also other things that we are trying to do, such as use radiation therapy to unmask new antigens with the expectations that unmasking new antigens will also stimulate the anti tumor immune response.
發現能夠預測治療應答的生物標誌物至關重要
【國際肝病】
基於生物標誌物的新策略如何推動肝癌的個人化治療，以及如何透過這些策略來預測和評估個人化治療的機會和效果？
Lewis R. Roberts教授： 癌癥治療中，最重要的是認識到幾乎每種療法都只對部份患者或腫瘤產生應答。如果我們能發現能夠對特定治療的應答進行預測的生物標誌物，就能對特定患者給予最有效的靶向治療。因此，如果我們發現能夠預測治療應答的生物標誌物，對於增強治療應答是至關重要的，從而可以為每位患者提供最佳的治療。
英文原文
<Hepatology Digest>: How do novel biomarker-based strategies facilitate personalized treatment in HCC, and how can these strategies be used to predict and evaluate the opportunities and efficacy of personalized treatment?
Dr. Lewis Roberts: One of the most important things in cancer therapy is to recognize that for almost every therapy only a proportion of people or tumors will respond. And if we can identify the biomarkers that are predictive of response to a particular therapy, then we can give the most efficient in targeting therapy for particular patients that is most effective for them. And so I think that working to identify biomarkers, predictable responses, is critical to allow us to expand the response of treatments and to allow us to provide optimal treatment for each individual.
