In Situ Vaccination as a Strategy to Modulate the Immune Microenvironment of Hepatocellular Carcinoma.
In Situ Vaccination as a Strategy to Modulate the Immune Microenvironment of Hepatocellular Carcinoma.
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DOI：
10.3389/fimmu.2021.650486
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发表时间：
2021
影响因子：
7.3
通讯作者：
Hammerich L
中科院分区：
文献类型：
--
作者：
Lurje I;Werner W;Mohr R;Roderburg C;Tacke F;Hammerich L
肝细胞癌是一种高度常见的恶性肿瘤，它发生在慢性肝病患者以及系统和肝脏免疫功能失调的患者中。肿瘤微环境由肿瘤相关巨噬细胞()、肿瘤相关成纤维细胞(CAF)、调节性T细胞(Treg)和髓源性抑制细胞(MDSC)组成，是介导免疫逃避和治疗抵抗的中枢细胞。这些细胞类型之间的相互作用通常会导致抗原提呈不足，从而阻碍有效的抗肿瘤免疫反应。原位疫苗利用肿瘤作为抗原源，并实施顺序免疫调节，以产生系统和持久的抗肿瘤免疫。因此，原位疫苗有望从肝癌细胞逃避抗原呈递并抑制T细胞反应的免疫抑制环境转变为富含激活的细胞毒细胞的免疫刺激环境。原位免疫的关键步骤包括诱导肿瘤细胞的免疫原性死亡，以树突状细胞为重点的抗原提呈细胞的募集，其负载和成熟，以及随后的CD8+T细胞的交叉启动，以确保对肿瘤细胞的细胞毒活性。已经提出了几种原位疫苗方法，疫苗方案包括溶瘤病毒、Flt3L、GM-CSF和TLR激动剂。此外，在肝细胞癌和其他肿瘤实体中，已建议联合使用检查点抑制剂。本文将对各种原位疫苗治疗肝癌的策略进行综述，重点介绍原位疫苗治疗肝癌的潜力和缺陷。
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. In situ vaccines harness the tumor as the source of antigens and implement sequential immunomodulation to generate systemic and lasting antitumor immunity. Thus, in situ 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 in situ 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 in situ 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 in situ vaccine strategies for HCC, highlighting the potentials and pitfalls of in situ vaccines to treat liver cancer.
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DOI：
10.1084/jem.20050915
发表时间：
2005-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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通讯作者：
Kroemer G
DOI：
10.1016/j.bpg.2014.08.007
发表时间：
2014-10-01
影响因子：
3.2
作者：
Bosetti, Cristina;Turati, Federica;La Vecchia, Carlo
通讯作者：
La Vecchia, Carlo
DOI：
10.4049/jimmunol.0803404
发表时间：
2009-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
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通讯作者：
DeMatteo RP
影响因子：
11.5
作者：
Bekaii-Saab, Tanios;Wesolowski, Robert;Kaumaya, Pravin T. P.
通讯作者：
Kaumaya, Pravin T. P.
影响因子：
5.4
作者：
Abdullahi, Sarah;Jaekel, Melanie;Altomonte, Jennifer
通讯作者：
Altomonte, Jennifer