Kamya Sankar, Ashley N Pearson, Tejaswi Worlikar, Matthew D Perricone, Erin A Holcomb, Mishal Mendiratta-Lala, Zhen Xu, Neil Bhowmick, Michael D Green
{"title":"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。","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":null,"pages":null},"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":"{\"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\":null,\"pages\":null},\"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}","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}
Impact of immune tolerance mechanisms on the efficacy of immunotherapy in primary and secondary liver cancers.
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.
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.