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第74届美国肝病研究学会年会（AASLD 2023）刚刚于美国波士顿闭幕。四大前沿讲座之一——“Leon Schiff State of the Art: Personalized Approach to HCC”上，美国妙佑医疗国际（Mayo Clinic）胃肠肝病部Lewis R. Roberts 教授不仅介绍了肝细胞癌（HCC）精准治疗的原则，而且重点分享了如何从肿瘤免疫微环境视角考虑个体化治疗。《国际肝病》记者有幸邀请到Lewis R. Roberts 教授，简要分享肿瘤微环境对HCC发生和发展的影响、联合治疗的主要作用机制，以及如何为每位患者提供最佳治疗。访谈视频和中英文对照访谈原稿整理如下。

 

肿瘤微环境影响HCC发生和发展的机制

 

《国际肝病》

肝癌的免疫微环境如何影响精准治疗的效果？

 

Lewis R. Roberts教授：作为对肿瘤发生和发展的反应，形成了肿瘤微环境，肿瘤为了不断进展，必须能够逃避倾向于消除肿瘤的自然免疫应答，因此，肿瘤微环境中的多种元素，包括血管的变化以及我们称之为免疫检查点的变化，试图抑制免疫反应，这些分子会形成癌细胞的屏障，阻止免疫细胞攻击它们。

 

英文原文
 

: 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联合治疗的主要机制及策略

 

《国际肝病》

联合治疗在改善肝癌肿瘤反应方面的具体效果如何，以及如何确定最佳的治疗组合和时机？

 

Lewis R. Roberts教授：特别是在HCC中，已经非常明确，例如贝伐珠单抗等抑制VEGF受体的药物，通过调节VEGF受体通路，实际上是对抗肿瘤的抗免疫效应，它们不仅阻断了肿瘤的血管生成，还阻断了通过VEGF介导的免疫应答抑制。因此，我们可以使用这些药物，并且与例如PD-1和PDL-1抑制剂等更多的标准免疫检查点抑制剂联合应用，进一步阻断肿瘤的抑制作用。

 

英文原文

 

: 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.

 

对HCC治疗前景的期待

 

《国际肝病》

免疫治疗在HCC患者的预后中起着越来越重要的作用。您如何看待这一趋势，并如何将其应用于改善患者的治疗结果？

 

Lewis R. Roberts教授：随着我们对HCC的肿瘤微环境，尤其是免疫微环境的深入了解，我们期望确定HCC其他重要的检查点，从而可以开发药物或联合治疗，包括针对这些其他检查点的治疗药物。我们也在尝试其他方法，比如应用放射疗法，使肿瘤的新抗原显露出来，期望显露出来的新抗原也会刺激抗肿瘤的免疫反应。

 

英文原文

 

: 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.

 

发现能够预测治疗应答的生物标志物至关重要

 

《国际肝病》

基于生物标志物的新策略如何推动肝癌的个性化治疗，以及如何通过这些策略来预测和评估个性化治疗的机会和效果？

 

Lewis R. Roberts教授：癌症治疗中，最重要的是认识到几乎每种疗法都只对部分患者或肿瘤产生应答。如果我们能发现能够对特定治疗的应答进行预测的生物标志物，就能对特定患者给予最有效的靶向治疗。因此，如果我们发现能够预测治疗应答的生物标志物，对于增强治疗应答是至关重要的，从而可以为每位患者提供最佳的治疗。

 

英文原文

 

: 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.

 

 

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