Vella Gerlanda, Hua Yichao, Bergers Gabriele
Laboratory of Tumor Microenvironment and Therapeutic Resistance, Department of Oncology, VIB-Center for Cancer Biology, KU Leuven, Leuven, Belgium.
Laboratory of Tumor Microenvironment and Therapeutic Resistance, Department of Oncology, VIB-Center for Cancer Biology, KU Leuven, Leuven, Belgium.
Cancer Cell. 2023 Mar 13;41(3):527-545. doi: 10.1016/j.ccell.2023.02.002. Epub 2023 Feb 23.
The lack of sufficient intratumoral CD8 T lymphocytes is a significant obstacle to effective immunotherapy in cancer. High endothelial venules (HEVs) are organ-specific and specialized postcapillary venules uniquely poised to facilitate the transmigration of lymphocytes to lymph nodes (LNs) and other secondary lymphoid organs (SLOs). HEVs can also form in human and murine cancer (tumor HEVs [TU-HEVs]) and contribute to the generation of diffuse T cell-enriched aggregates or tertiary lymphoid structures (TLSs), which are commonly associated with a good prognosis. Thus, therapeutic induction of TU-HEVs may provide attractive avenues to induce and sustain the efficacy of immunotherapies by overcoming the major restriction of T cell exclusion from the tumor microenvironment. In this review, we provide current insight into the commonalities and discrepancies of HEV formation and regulation in LNs and tumors and discuss the specific function and significance of TU-HEVs in eliciting, predicting, and aiding anti-tumoral immunity.
肿瘤内缺乏足够的CD8 T淋巴细胞是癌症有效免疫治疗的重大障碍。高内皮微静脉（HEV）是器官特异性的特化毛细血管后微静脉，具有独特的条件来促进淋巴细胞迁移至淋巴结（LN）和其他二级淋巴器官（SLO）。HEV也可在人类和小鼠肿瘤中形成（肿瘤HEV [TU-HEV]），并有助于产生弥漫性富含T细胞的聚集物或三级淋巴结构（TLS），这些通常与良好的预后相关。因此，通过克服肿瘤微环境中T细胞排除这一主要限制，TU-HEV的治疗性诱导可能为诱导和维持免疫治疗的疗效提供有吸引力的途径。在这篇综述中，我们阐述了目前对LN和肿瘤中HEV形成与调控的共性和差异的见解，并讨论了TU-HEV在引发、预测和辅助抗肿瘤免疫方面的特定功能和意义。
