西班牙纳瓦拉大学Ignacio Melero和Álvaro Teijeira团队合作取得新进展。他们发现肿瘤产生的CXCR1和CXCR2趋化因子受体激动剂诱导嗜中性粒细胞胞外陷阱（NETs）并干扰免疫细胞毒性。这一研究成果发表在2020年4月13日出版的《免疫学》杂志上。

CXCR1和CXCR2激动剂被证明是癌症促进NETosis的主要中间体。NET缠绕并包裹肿瘤细胞，并通过阻止免疫细胞与周围靶细胞之间的接触，使其免受CD8 + T细胞和自然杀伤（NK）以及细胞介导的细胞毒性作用。

NETs保护肿瘤细胞免受细胞毒性，这是小鼠癌症转移成功的基础，而精氨酸脱亚氨酶4（PAD4）抑制剂的免疫治疗协同作用，则可通过免疫检验点抑制剂抑制NETosis。活体显微镜检查提供了中性粒细胞NET干扰胞质细胞毒性T淋巴细胞（CTL）和NK细胞与肿瘤细胞接触的证据。

据悉，中性粒细胞在携带癌症的宿主中扩展并丰富。在CXCR1和CXCR2趋化因子受体激动剂和其他趋化因子的影响下，癌症患者的肿瘤、嗜中性粒细胞和粒细胞髓样来源的抑制细胞（MDSC）产生了它们的NETs。

附：英文原文

Title: CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity

Author: álvaro Teijeira, Saray Garasa, María Gato, Carlos Alfaro, Itziar Migueliz, Assunta Cirella, Carlos de Andrea, Maria Carmen Ochoa, Itziar Otano, Iaki Etxeberria, Maria Pilar Andueza, Celia P. Nieto, Leyre Resano, Arantza Azpilikueta, Marcello Allegretti, Maria de Pizzol, Mariano Ponz-Sarvisé, Ana Rouzaut, Miguel F. Sanmamed, Kurt Schalper, Michael Carleton, Mario Mellado, María E. Rodriguez-Ruiz, Pedro Berraondo, Jose L. Perez-Gracia, Ignacio Melero

Issue&Volume: 2020-04-13

Abstract: Neutrophils are expanded and abundant in cancer-bearing hosts. Under the influenceof CXCR1 and CXCR2 chemokine receptor agonists and other chemotactic factors producedby tumors, neutrophils, and granulocytic myeloid-derived suppressor cells (MDSCs)from cancer patients extrude their neutrophil extracellular traps (NETs). In our hands,CXCR1 and CXCR2 agonists proved to be the major mediators of cancer-promoted NETosis.NETs wrap and coat tumor cells and shield them from cytotoxicity, as mediated by CD8+ T cells and natural killer (NK) cells, by obstructing contact between immune cellsand the surrounding target cells. Tumor cells protected from cytotoxicity by NETsunderlie successful cancer metastases in mice and the immunotherapeutic synergy ofprotein arginine deiminase 4 (PAD4) inhibitors, which curtail NETosis with immunecheckpoint inhibitors. Intravital microscopy provides evidence of neutrophil NETsinterfering cytolytic cytotoxic T lymphocytes (CTLs) and NK cell contacts with tumorcells.

DOI: 10.1016/j.immuni.2020.03.001

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30089-3