Targeting tumor-associated macrophages to overcome immune checkpoint inhibitor resistance in hepatocellular carcinoma.

IF 12.8 1区 医学 Q1 ONCOLOGY
Fen Liu, Xianying Li, Yiming Zhang, Shan Ge, Zhan Shi, Qingbin Liu, Shulong Jiang
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引用次数: 0

Abstract

Hepatocellular carcinoma (HCC) remains a critical global health concern, particularly in regions with high endemicity of hepatitis B, hepatitis C, and non-alcoholic fatty liver disease. Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has emerged as a promising therapeutic strategy for advanced HCC. Despite encouraging results, primary and acquired resistance to ICIs continues to pose significant challenges in clinical practice. Recent research has identified tumor-associated macrophages (TAMs) as key contributors to immune evasion and ICI resistance in HCC, primarily through polarization to the M2 phenotype. M2-polarized TAMs secrete a range of immunosuppressive cytokines that inhibit T cell activation and promote tumor progression through processes such as angiogenesis and epithelial-mesenchymal transition. These mechanisms compromise the efficacy of ICIs and facilitate tumor expansion and metastasis. This review summarizes the role of TAM-related signaling pathways in driving immune evasion and ICI resistance in HCC, with particular emphasis on the contribution of TAM surface receptors and chemokines in immune suppression. Additionally, the review highlights emerging insights into TAM metabolic reprogramming and transcriptional regulation, which have been closely linked to ICI resistance. Furthermore, we explore promising therapeutic strategies targeting TAMs and their associated signaling pathways to enhance ICI efficacy in HCC. Integrating these novel approaches could potentially overcome TAM-driven immune evasion and ICI resistance, boosting the efficacy of immunotherapy and improving patient prognosis in HCC.

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靶向肿瘤相关巨噬细胞克服肝细胞癌免疫检查点抑制剂耐药性
肝细胞癌(HCC)仍然是一个重要的全球健康问题,特别是在乙型肝炎、丙型肝炎和非酒精性脂肪性肝病高发地区。免疫疗法,特别是免疫检查点抑制剂(ICIs),已成为晚期HCC的一种有前景的治疗策略。尽管取得了令人鼓舞的结果,但对ICIs的原发性和获得性耐药继续在临床实践中构成重大挑战。最近的研究发现,肿瘤相关巨噬细胞(tam)是HCC中免疫逃避和ICI抵抗的关键因素,主要是通过向M2表型极化。m2极化tam分泌一系列免疫抑制细胞因子,通过血管生成和上皮-间质转化等过程抑制T细胞活化并促进肿瘤进展。这些机制损害了ICIs的疗效,促进了肿瘤的扩张和转移。本文综述了TAM相关信号通路在HCC中驱动免疫逃避和ICI耐药中的作用,重点介绍了TAM表面受体和趋化因子在免疫抑制中的作用。此外,该综述还强调了TAM代谢重编程和转录调控的新见解,这与ICI耐药性密切相关。此外,我们还探索了针对tam及其相关信号通路的有希望的治疗策略,以增强ICI在HCC中的疗效。整合这些新方法可以潜在地克服tam驱动的免疫逃避和ICI耐药性,提高免疫治疗的疗效,改善HCC患者的预后。
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来源期刊
CiteScore
18.20
自引率
1.80%
发文量
333
审稿时长
1 months
期刊介绍: The Journal of Experimental & Clinical Cancer Research is an esteemed peer-reviewed publication that focuses on cancer research, encompassing everything from fundamental discoveries to practical applications. We welcome submissions that showcase groundbreaking advancements in the field of cancer research, especially those that bridge the gap between laboratory findings and clinical implementation. Our goal is to foster a deeper understanding of cancer, improve prevention and detection strategies, facilitate accurate diagnosis, and enhance treatment options. We are particularly interested in manuscripts that shed light on the mechanisms behind the development and progression of cancer, including metastasis. Additionally, we encourage submissions that explore molecular alterations or biomarkers that can help predict the efficacy of different treatments or identify drug resistance. Translational research related to targeted therapies, personalized medicine, tumor immunotherapy, and innovative approaches applicable to clinical investigations are also of great interest to us. We provide a platform for the dissemination of large-scale molecular characterizations of human tumors and encourage researchers to share their insights, discoveries, and methodologies with the wider scientific community. By publishing high-quality research articles, reviews, and commentaries, the Journal of Experimental & Clinical Cancer Research strives to contribute to the continuous improvement of cancer care and make a meaningful impact on patients' lives.
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