Abstract: Hepatocellular carcinoma (HCC) is the most common liver cancer and one of the leading causes of cancer-related deaths in the world. Multiple immunotherapeutic approaches have been investigated to date, and immunotherapy has become the new standard of care therapy in HCC. However, the current role of immunotherapy in HCC remains non-curative. Given this context, a high priority for oncology is understanding the biomarkers that predict clinical response to immunotherapy, have the potential to improve patient selection to maximize the clinical benefit, and spare unnecessary toxicity. In this review, we summarize the key predictive and prognostic biomarkers investigated in immunotherapy clinical trials in HCC and the emerging biomarkers to serve as a roadmap for future clinical trials. Biomarkers from tumoral tissues including PDL-1 expression, tissue infiltrating lymphocytes, tumor mutational burden (TMB) and specific immune signatures, and from peripheral blood including neutrophil-to-lymphocytes ratio, platelet-to-lymphocytes ratio, circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and specific cytokines, along with gut microbiota are among the studied biomarkers to date in the HCC era. More integrative approaches, including mathematical biomarkers to predict immunotherapy outcomes, are yet to be studied in HCC.

Keywords: hepatocellular carcinoma, immunotherapy, biomarker


中文翻译：

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肝细胞癌免疫治疗生物标志物的现状和未来方向

【摘要】：肝细胞癌(HCC)是最常见的肝癌,也是全球癌症相关死亡的主要原因之一。迄今为止，多种免疫治疗方法已得到研究，免疫治疗已成为 HCC 护理治疗的新标准。然而，目前免疫疗法在 HCC 中的作用仍然是非治愈性的。鉴于这种背景，肿瘤学的首要任务是了解预测免疫治疗临床反应的生物标志物，有可能改善患者选择，以最大限度地提高临床效益，并避免不必要的毒性。在这篇综述中，我们总结了 HCC 免疫治疗临床试验中研究的关键预测和预后生物标志物以及新兴生物标志物，作为未来临床试验的路线图。来自肿瘤组织的生物标志物，包括 PDL-1 表达、组织浸润淋巴细胞、肿瘤突变负荷 (TMB) 和特异性免疫特征，以及来自外周血的生物标志物，包括中性粒细胞与淋巴细胞比率、血小板与淋巴细胞比率、循环肿瘤 DNA (ctDNA) 、循环肿瘤细胞 (CTC) 和特定细胞因子以及肠道微生物群是迄今为止在 HCC 时代研究的生物标志物之一。更综合的方法，包括预测免疫治疗结果的数学生物标志物，还有待在 HCC 中进行研究。

关键词:肝细胞癌, 免疫治疗, 生物标志物