德国汉堡-埃彭多夫大学医学中心Samuel Huber和Anastasios D. Giannou共同合作，近期取得重要工作进展。他们研究发现组织驻留iNKT17细胞通过白细胞介素22促进肝转移中的癌细胞外渗。相关论文2023年1月10日在线发表于《免疫》杂志上。

据介绍，在转移过程中，癌细胞会侵入、内渗、进入循环、外渗和定植靶器官。

研究人员探讨了白细胞介素-22（IL-22）在转移中的作用。免疫细胞来源的IL-22作用于上皮组织，促进组织损伤的再生和愈合，但它也与恶性肿瘤相关。II-22缺陷小鼠和用IL-22抗体治疗的小鼠被保护免于结肠癌来源的肝和肺转移形成，而IL-22的过度表达促进了转移。

从机理上讲，IL-22作用于内皮细胞，通过诱导内皮氨基肽酶N促进内皮细胞通透性和癌细胞迁移。多参数流式细胞术和对癌细胞外渗进入肝脏期间分离的免疫细胞的单细胞测序显示iNKT17细胞是IL-22的来源。iNKT细胞缺陷小鼠表现出减少的转移，这是被注射野生型而不是被Il22缺陷的不变自然杀伤T（iNKT）细胞所逆转。产生IL-22的iNKT细胞促进转移是组织驻留的，正如异种共生所证明的那样。因此，IL-22可能是预防转移的治疗靶点。

附：英文原文

Title: Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22

Author: Anastasios D. Giannou, Jan Kempski, Ahmad Mustafa Shiri, Jran Lücke, Tao Zhang, Lilan Zhao, Dimitra E. Zazara, Filippo Cortesi, Kristoffer Riecken, Maria Carolina Amezcua Vesely, Jun Siong Low, Hao Xu, Eleanna Kaffe, Laura Garcia-Perez, Theodora Agalioti, Yoshito Yamada, Wolfgang Jungraithmayr, Ehud Zigmond, Karl-Frederick Karstens, Babett Steglich, Jonas Wagner, Leonie Konczalla, Antonella Carambia, Kornelius Schulze, Johann von Felden, Peter May, Daria Briukhovetska, Tanja Bedke, Leonie Brockmann, Sarah Starzonek, Tobias Lange, Claudia Koch, Sabine Riethdorf, Penelope Pelczar, Marius Bttcher, Morsal Sabihi, Francis J. Huber, Matthias Reeh, Julia Kristin Grass, Ramez Wahib, Hannes Seese, Bjrn-Ole Stüben, Mohammad Fard-Aghaie, Anna Duprée, Pasquale Scognamiglio, Gabriel Plitzko, Jan Meiners, Shiwa Soukou, Agnes Wittek, Caroline Manthey, Ioannis C. Maroulis, Petra C. Arck, Daniel Perez, Bin Gao, Sotirios G. Zarogiannis

Issue&Volume: 2023/01/10

Abstract: During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice and mice treated with an IL-22 antibody were protected from colon-cancer-derived liver and lung metastasis formation, while overexpression of IL-22 promoted metastasis. Mechanistically, IL-22 acted on endothelial cells, promoting endothelial permeability and cancer cell transmigration via induction of endothelial aminopeptidase N. Multi-parameter flow cytometry and single-cell sequencing of immune cells isolated during cancer cell extravasation into the liver revealed iNKT17 cells as source of IL-22. iNKT-cell-deficient mice exhibited reduced metastases, which was reversed by injection of wild type, but not Il22-deficient, invariant natural killer T (iNKT) cells. IL-22-producing iNKT cells promoting metastasis were tissue resident, as demonstrated by parabiosis. Thus, IL-22 may present a therapeutic target for prevention of metastasis.

DOI: 10.1016/j.immuni.2022.12.014

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00650-1