用于肝胆恶性肿瘤免疫治疗反应的生物标志物。

Biomarkers for response to immunotherapy in hepatobiliary malignancies.

机构信息

Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Fudan University, Shanghai 200040, China.

出版信息

Hepatobiliary Pancreat Dis Int. 2022 Oct;21(5):413-419. doi: 10.1016/j.hbpd.2022.08.002. Epub 2022 Aug 8.

DOI:10.1016/j.hbpd.2022.08.002

PMID:35973935

Abstract

BACKGROUND

The advent of immune checkpoint inhibitors (ICIs) has revolutionized the therapeutic options of hepatobiliary malignancies. However, the clinical benefit provided by immunotherapy seems limited to a small subgroup of patients with hepatobiliary malignancies. The identification of reliable predictors of the response to immunotherapy is urgently needed.

DATA SOURCES

Literature search was conducted in PubMed for relevant articles published up to May 2022. Information of clinical trials was obtained from https://clinicaltrials.gov/.

RESULTS

Biomarkers for ICI response of hepatobiliary malignancies remain in the exploration stage and lack compelling evidence. Tumor programmed death-ligand 1 (PD-L1) expression is the most widely studied biomarker in hepatocellular carcinoma (HCC) and biliary tract cancers (BTCs), but there are conflicting results on its predictive potential. Tumor mutational burden (TMB) is generally low both in HCC and BTCs, and the clinical trials of TMB are rare in hepatobiliary malignancies. Promisingly, mismatch repair deficiency (dMMR)/high microsatellite instability (MSI-H) may be a predictive biomarker of response to anti-PD-1 therapy in BTCs. Furthermore, some emerging biomarkers, such as gut microbiota, show predictive potential in the preliminary studies. Radiomics and liquid-biopsy biomarkers, including circulating tumor cells, circulating tumor DNA (ctDNA) and exosomal PD-L1 provide a quick and non-invasive approach for monitoring the ICI response, showing a new promising direction.

CONCLUSIONS

Multiple potential biomarkers for predicting ICI response of hepatobiliary malignancies have been explored and tried to apply in clinic. Yet there is no robust evidence to prove their clinical value in predicting immunotherapeutic response for patients with hepatobiliary malignancies. The identification of predictors for response to ICIs is an urgent need and major challenge. Further studies are warranted to validate the role of emerging biomarkers in predicting immunotherapeutic responses.

摘要

背景

免疫检查点抑制剂（ICIs）的出现彻底改变了肝胆恶性肿瘤的治疗选择。然而，免疫疗法提供的临床获益似乎仅限于一小部分肝胆恶性肿瘤患者。迫切需要确定可靠的免疫治疗反应预测因子。

资料来源

在 PubMed 上进行了文献检索，以获取截至 2022 年 5 月发表的相关文章。临床试验信息来自 https://clinicaltrials.gov/。

结果

肝胆恶性肿瘤的 ICI 反应生物标志物仍处于探索阶段，缺乏确凿的证据。肿瘤程序性死亡配体 1（PD-L1）表达是肝细胞癌（HCC）和胆管癌（BTC）中研究最广泛的生物标志物，但关于其预测潜力的结果存在矛盾。肿瘤突变负担（TMB）在 HCC 和 BTC 中普遍较低，肝胆恶性肿瘤中 TMB 的临床试验很少。有希望的是，错配修复缺陷（dMMR）/高微卫星不稳定性（MSI-H）可能是 BTC 对抗 PD-1 治疗反应的预测生物标志物。此外，一些新兴的生物标志物，如肠道微生物群，在初步研究中显示出预测潜力。放射组学和液体活检生物标志物，包括循环肿瘤细胞、循环肿瘤 DNA（ctDNA）和外泌体 PD-L1，为监测 ICI 反应提供了快速、非侵入性的方法，显示出一个新的有前途的方向。