Impact of immune tolerance mechanisms on the efficacy of immunotherapy in primary and secondary liver cancers.

IF 3 4区医学 Q1 Medicine

Translational gastroenterology and hepatology Pub Date : 2023-01-01 DOI:10.21037/tgh-23-11

Kamya Sankar, Ashley N Pearson, Tejaswi Worlikar, Matthew D Perricone, Erin A Holcomb, Mishal Mendiratta-Lala, Zhen Xu, Neil Bhowmick, Michael D Green

{"title":"Impact of immune tolerance mechanisms on the efficacy of immunotherapy in primary and secondary liver cancers.","authors":"Kamya Sankar, Ashley N Pearson, Tejaswi Worlikar, Matthew D Perricone, Erin A Holcomb, Mishal Mendiratta-Lala, Zhen Xu, Neil Bhowmick, Michael D Green","doi":"10.21037/tgh-23-11","DOIUrl":null,"url":null,"abstract":"<p><p>The liver is a functionally unique organ with an immunosuppressive microenvironment. The liver is the sixth most common site of primary cancer in humans and is a frequent site of metastasis from other solid tumors. The development of effective therapies for primary and metastatic liver cancer has been challenging due to the complex metabolic and immune microenvironment of the liver. The liver tumor microenvironment (TME) in primary and secondary (metastatic) liver cancers is heterogenous and consists of unique immune and stromal cell populations. Crosstalk between these cell populations and tumor cells creates an immunosuppressive microenvironment within the liver which potentiates cancer progression. Immune checkpoint inhibitors (ICIs) are now clinically approved for the management of primary and secondary liver cancer and can partially overcome liver immune tolerance, but their efficacy is limited. In this review, we describe the liver microenvironment and the use of immunotherapy in primary and secondary liver cancer. We discuss emerging combination strategies utilizing locoregional and systemic therapy approaches which may enhance efficacy of immunotherapy in primary and secondary liver cancer. A deeper understanding of the immunosuppressive microenvironment of the liver will inform novel therapies and therapeutic combinations in order to improve outcomes of patients with primary and secondary liver cancer.</p>","PeriodicalId":23267,"journal":{"name":"Translational gastroenterology and hepatology","volume":"8 ","pages":"29"},"PeriodicalIF":3.0000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5c/58/tgh-08-23-11.PMC10432235.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational gastroenterology and hepatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tgh-23-11","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

Abstract

The liver is a functionally unique organ with an immunosuppressive microenvironment. The liver is the sixth most common site of primary cancer in humans and is a frequent site of metastasis from other solid tumors. The development of effective therapies for primary and metastatic liver cancer has been challenging due to the complex metabolic and immune microenvironment of the liver. The liver tumor microenvironment (TME) in primary and secondary (metastatic) liver cancers is heterogenous and consists of unique immune and stromal cell populations. Crosstalk between these cell populations and tumor cells creates an immunosuppressive microenvironment within the liver which potentiates cancer progression. Immune checkpoint inhibitors (ICIs) are now clinically approved for the management of primary and secondary liver cancer and can partially overcome liver immune tolerance, but their efficacy is limited. In this review, we describe the liver microenvironment and the use of immunotherapy in primary and secondary liver cancer. We discuss emerging combination strategies utilizing locoregional and systemic therapy approaches which may enhance efficacy of immunotherapy in primary and secondary liver cancer. A deeper understanding of the immunosuppressive microenvironment of the liver will inform novel therapies and therapeutic combinations in order to improve outcomes of patients with primary and secondary liver cancer.

Abstract Image

查看原文本刊更多论文

免疫耐受机制对原发性和继发性肝癌免疫治疗疗效的影响。

肝脏是一个功能独特的器官，具有免疫抑制微环境。肝脏是人类原发癌症的第六大常见部位，也是其他实体肿瘤转移的常见部位。由于肝脏复杂的代谢和免疫微环境，开发有效的治疗原发性和转移性肝癌的方法一直具有挑战性。原发性和继发性(转移性)肝癌的肝肿瘤微环境(TME)是异质的，由独特的免疫和基质细胞群组成。这些细胞群和肿瘤细胞之间的串扰在肝脏内创造了一个免疫抑制的微环境，从而加速了癌症的进展。免疫检查点抑制剂(ICIs)现已被临床批准用于原发性和继发性肝癌的治疗，并且可以部分克服肝脏免疫耐受，但其疗效有限。在这篇综述中，我们描述了肝脏微环境和免疫治疗在原发性和继发性肝癌中的应用。我们讨论了利用局部和全身治疗方法的新兴联合策略，这可能会提高原发性和继发性肝癌免疫治疗的疗效。对肝脏免疫抑制微环境的深入了解将为新的治疗方法和治疗组合提供信息，从而改善原发性和继发性肝癌患者的预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Translational gastroenterology and hepatology Medicine-Gastroenterology

CiteScore

8.20

自引率

0.00%

发文量

期刊介绍： Translational Gastroenterology and Hepatology (Transl Gastroenterol Hepatol; TGH; Online ISSN 2415-1289) is an open-access, peer-reviewed online journal that focuses on cutting-edge findings in the field of translational research in gastroenterology and hepatology and provides current and practical information on diagnosis, prevention and clinical investigations of gastrointestinal, pancreas, gallbladder and hepatic diseases. Specific areas of interest include, but not limited to, multimodality therapy, biomarkers, imaging, biology, pathology, and technical advances related to gastrointestinal and hepatic diseases. Contributions pertinent to gastroenterology and hepatology are also included from related fields such as nutrition, surgery, public health, human genetics, basic sciences, education, sociology, and nursing.