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接种疫苗作为调节肝癌免疫微环境的策略。

Vaccination as a Strategy to Modulate the Immune Microenvironment of Hepatocellular Carcinoma.

机构信息

Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Berlin, Germany.

Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

出版信息

Front Immunol. 2021 May 7;12:650486. doi: 10.3389/fimmu.2021.650486. eCollection 2021.

Abstract

Hepatocellular Carcinoma (HCC) is a highly prevalent malignancy that develops in patients with chronic liver diseases and dysregulated systemic and hepatic immunity. The tumor microenvironment (TME) contains tumor-associated macrophages (TAM), cancer-associated fibroblasts (CAF), regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) and is central to mediating immune evasion and resistance to therapy. The interplay between these cells types often leads to insufficient antigen presentation, preventing effective anti-tumor immune responses. vaccines harness the tumor as the source of antigens and implement sequential immunomodulation to generate systemic and lasting antitumor immunity. Thus, vaccines hold the promise to induce a switch from an immunosuppressive environment where HCC cells evade antigen presentation and suppress T cell responses towards an immunostimulatory environment enriched for activated cytotoxic cells. Pivotal steps of vaccination include the induction of immunogenic cell death of tumor cells, a recruitment of antigen-presenting cells with a focus on dendritic cells, their loading and maturation and a subsequent cross-priming of CD8+ T cells to ensure cytotoxic activity against tumor cells. Several vaccine approaches have been suggested, with vaccine regimens including oncolytic viruses, Flt3L, GM-CSF and TLR agonists. Moreover, combinations with checkpoint inhibitors have been suggested in HCC and other tumor entities. This review will give an overview of various vaccine strategies for HCC, highlighting the potentials and pitfalls of vaccines to treat liver cancer.

摘要

肝细胞癌(HCC)是一种在慢性肝病和系统性及肝脏免疫失调患者中发生的高度流行的恶性肿瘤。肿瘤微环境(TME)包含肿瘤相关巨噬细胞(TAM)、癌相关成纤维细胞(CAF)、调节性 T 细胞(Treg)和髓系来源的抑制细胞(MDSC),是介导免疫逃逸和治疗耐药的核心。这些细胞类型之间的相互作用常常导致抗原呈递不足,阻止有效的抗肿瘤免疫反应。疫苗利用肿瘤作为抗原来源,并实施序贯免疫调节,以产生全身和持久的抗肿瘤免疫。因此,疫苗有望诱导从免疫抑制环境向富含激活的细胞毒性细胞的免疫刺激环境转变,在该环境中 HCC 细胞逃避抗原呈递并抑制 T 细胞反应。疫苗接种的关键步骤包括诱导肿瘤细胞的免疫原性细胞死亡、招募以树突状细胞为重点的抗原呈递细胞、它们的负载和成熟以及随后对 CD8+T 细胞进行交叉致敏,以确保对肿瘤细胞的细胞毒性活性。已经提出了几种疫苗方法,疫苗方案包括溶瘤病毒、Flt3L、GM-CSF 和 TLR 激动剂。此外,在 HCC 和其他肿瘤实体中,已经提出了与检查点抑制剂联合使用的方案。这篇综述将概述 HCC 的各种疫苗策略,强调疫苗治疗肝癌的潜力和陷阱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9b7/8137829/6ad8f7064589/fimmu-12-650486-g001.jpg

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