小柯机器人

法国图卢兹大学Jean-Philippe Girard课题组发现，肿瘤相关的高内皮静脉介导淋巴细胞进入肿瘤并预测PD-1+CTLA-4联合免疫治疗的反应。相关论文于2022年2月3日在线发表在《癌细胞》杂志上。

研究人员在小鼠模型中显示，肿瘤相关的高内皮静脉（TA-HEV）是淋巴细胞在基线和接受抗PD-1/抗CTLA-4免疫检查点阻断治疗（ICB）时进入肿瘤的主要场所。TA-HEV内皮细胞（TA-HEC）来源于毛细血管后静脉，共同表达MECA-79⁺ HEV唾液黏蛋白和E/P-选择素，并与各种T细胞亚群的归巢和渗入肿瘤有关。活体显微镜进一步显示，TA-HEV是淋巴细胞停滞和外渗到ICB处理的肿瘤的主要部位。增加TA-HEV的频率和成熟度可增加肿瘤浸润性干细胞样CD8⁺ T细胞的比例，并改善ICB的疗效。

对93名转移性黑色素瘤患者的肿瘤活检分析显示，TA-HEV可预测抗PD-1/抗CTLA-4组合治疗后更好的反应和生存。这些研究对癌症免疫和免疫疗法中的淋巴细胞贩运机制提供了关键性的见解。

据悉，淋巴细胞进入肿瘤是抗肿瘤免疫和有效免疫治疗的关键。

附：英文原文

Title: Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy

Author: Assia Asrir, Claire Tardiveau, Juliette Coudert, Robin Laffont, Lucas Blanchard, Elisabeth Bellard, Krystle Veerman, Sarah Bettini, Fanny Lafouresse, Estefania Vina, Dorian Tarroux, Severine Roy, Isabelle Girault, Irma Molinaro, Frédéric Martins, Jean-Yves Scoazec, Nathalie Ortega, Caroline Robert, Jean-Philippe Girard

Issue&Volume: 2022-02-03

Abstract: Recruitment of lymphocytes into tumors is critical for anti-tumor immunity and efficacious immunotherapy. We show in murine models that tumor-associated high endothelial venules (TA-HEVs) are major sites of lymphocyte entry into tumors at baseline and upon treatment with anti-PD-1/anti-CTLA-4 immune checkpoint blockade (ICB). TA-HEV endothelial cells (TA-HECs) derive from post-capillary venules, co-express MECA-79+ HEV sialomucins and E/P-selectins, and are associated with homing and infiltration into tumors of various T cell subsets. Intravital microscopy further shows that TA-HEVs are the main sites of lymphocyte arrest and extravasation into ICB-treated tumors. Increasing TA-HEC frequency and maturation increases the proportion of tumor-infiltrating stem-like CD8+ T cells, and ameliorates ICB efficacy. Analysis of tumor biopsies from 93 patients with metastatic melanoma reveals that TA-HEVs are predictive of better response and survival upon treatment with anti-PD-1/anti-CTLA-4 combination. These studies provide critical insights into the mechanisms governing lymphocyte trafficking in cancer immunity and immunotherapy.

DOI: 10.1016/j.ccell.2022.01.002

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00004-6

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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