CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:High endothelial venules (HEVs) in immunity, inflammation and cancer.
High endothelial venules (HEVs) in immunity, inflammation and cancer.
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高内皮微静脉(HEVs)是介导淋巴细胞向淋巴结(LNs)及其他次级淋巴器官迁移的特化血管。通过支持淋巴细胞从血液中高效外渗,HEVs在淋巴细胞再循环和免疫监视中发挥重要作用,以应对外来入侵者(细菌和病毒感染)以及机体自身细胞的改变(癌症中的新抗原)。HEV网络在免疫刺激的LNs炎症过程中扩张,并在转移性和肿瘤引流LNs中发生深刻重塑。在许多人类炎症性和过敏性疾病(包括类风湿性关节炎、克罗恩病、过敏性鼻炎和哮喘)的慢性炎症部位,非淋巴组织中可诱导出表达高水平HEV特异性硫酸化MECA-79抗原的HEV样血管。此类血管被认为有助于慢性炎症的放大和维持。MECA-79+肿瘤相关HEVs(TA-HEVs)常见于人类肿瘤中CD3+T细胞富集区域或CD20+B细胞富集的第三淋巴结构(TLSs)中。TA-HEVs被认为在淋巴细胞进入肿瘤的过程中发挥重要作用,而这一过程对于成功的抗肿瘤免疫以及基于免疫检查点抑制剂、疫苗或过继性T细胞疗法的淋巴细胞介导的癌症免疫治疗至关重要。在本综述中,我们重点阐述HEVs在稳态、炎症和肿瘤引流淋巴结中的表型与功能,以及HEV样血管在慢性炎症性疾病中的表型与功能。
此外,我们还讨论TA-HEVs在人类癌症和小鼠肿瘤模型中的作用及调控。
High endothelial venules (HEVs) are specialized blood vessels mediating lymphocyte trafficking to lymph nodes (LNs) and other secondary lymphoid organs. By supporting high levels of lymphocyte extravasation from the blood, HEVs play an essential role in lymphocyte recirculation and immune surveillance for foreign invaders (bacterial and viral infections) and alterations in the body's own cells (neoantigens in cancer). The HEV network expands during inflammation in immune-stimulated LNs and is profoundly remodeled in metastatic and tumor-draining LNs. HEV-like blood vessels expressing high levels of the HEV-specific sulfated MECA-79 antigens are induced in non-lymphoid tissues at sites of chronic inflammation in many human inflammatory and allergic diseases, including rheumatoid arthritis, Crohn's disease, allergic rhinitis and asthma.
Such vessels are believed to contribute to the amplification and maintenance of chronic inflammation. MECA-79 + tumor-associated HEVs (TA-HEVs) are frequently found in human tumors in CD3 + T cell-rich areas or CD20 + B-cell rich tertiary lymphoid structures (TLSs).
TA-HEVs have been proposed to play important roles in lymphocyte entry into tumors, a process essential for successful antitumor immunity and lymphocyte-mediated cancer immunotherapy with immune checkpoint inhibitors, vaccines or adoptive T cell therapy. In this review, we highlight the phenotype and function of HEVs in homeostatic, inflamed and tumor-draining lymph nodes, and those of HEV-like blood vessels in chronic inflammatory diseases.
Furthermore, we discuss the role and regulation of TA-HEVs in human cancer and mouse tumor models.
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