德国慕尼黑大学附属医院Sebastian Kobold团队近期取得重要工作进展，他们研究发现T细胞来源的白细胞介素-22驱动癌细胞表达CD155以抑制NK细胞功能并促进转移。相关研究成果2023年1月10日在线发表于《免疫》杂志上。

据介绍，尽管T细胞可以发挥强大的抗肿瘤免疫功能，但在乳腺和肺部肿瘤中产生白细胞介素22（IL-22）的辅助T细胞（Th）亚群与患者的不良预后有关。

研究人员探讨了这些T细胞导致疾病的机制。在小鼠肺癌和乳腺癌模型中，Il22的结构和T细胞特异性缺失减少了转移，而不影响原发性肿瘤生长。癌细胞上IL-22受体的缺失减少了转移，其程度与IL-22缺陷小鼠相似。IL-22诱导CD155的高表达，CD155与NK细胞上的活化受体CD226结合。过度活化导致CD226数量减少，NK细胞功能受损，从而增加转移负担。IL-22信号传导也与人类数据集中CD155的表达相关，并且与不良的患者预后相关。

总之，这一发现揭示了一种由T细胞来源的IL-22激活的免疫抑制回路，它促进了肺转移。

附：英文原文

Title: T cell-derived interleukin-22 drives the expression of CD155 by cancer cells to suppress NK cell function and promote metastasis

Author: Daria Briukhovetska, Javier Suarez-Gosalvez, Cornelia Voigt, Anamarija Markota, Anastasios D. Giannou, Maryam Schübel, Jakob Jobst, Tao Zhang, Janina Drr, Florian Mrkl, Lina Majed, Philipp Jie Müller, Peter May, Adrian Gottschlich, Nicholas Tokarew, Jran Lücke, Arman Oner, Melanie Schwerdtfeger, David Andreu-Sanz, Ruth Grünmeier, Matthias Seifert, Stefanos Michaelides, Michael Hristov, Lars M. Knig, Bruno Loureiro Cadilha, Oleg Mikhaylov, Hans-Joachim Anders, Simon Rothenfusser, Richard A. Flavell, Daniela Cerezo-Wallis, Cristina Tejedo, María S. Soengas, Tobias Bald, Samuel Huber, Stefan Endres, Sebastian Kobold

Issue&Volume: 2023/01/10

Abstract: Although T cells can exert potent anti-tumor immunity, a subset of T helper (Th) cells producing interleukin-22 (IL-22) in breast and lung tumors is linked to dismal patient outcome. Here, we examined the mechanisms whereby these T cells contribute to disease. In murine models of lung and breast cancer, constitutional and T cell-specific deletion of Il22 reduced metastases without affecting primary tumor growth. Deletion of the IL-22 receptor on cancer cells decreases metastasis to a degree similar to that seen in IL-22-deficient mice. IL-22 induced high expression of CD155, which bound to the activating receptor CD226 on NK cells. Excessive activation led to decreased amounts of CD226 and functionally impaired NK cells, which elevated the metastatic burden. IL-22 signaling was also associated with CD155 expression in human datasets and with poor patient outcomes. Taken together, our findings reveal an immunosuppressive circuit activated by T cell-derived IL-22 that promotes lung metastasis.

DOI: 10.1016/j.immuni.2022.12.010

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00646-X