Department of Microbiology and Infection, Kochi Medical School, Kochi University, Nankoku, Kochi, 783-8505, Japan.
Division of Chemotherapy, Kindai University Faculty of Pharmacy, Higashi-Osaka, Osaka, 577-8502, Japan.
Cancer Lett. 2019 Jul 1;453:184-192. doi: 10.1016/j.canlet.2019.03.053. Epub 2019 Apr 3.
Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphomas associated with chronic inflammation (DLBCL-CI) develop in patients with chronic inflammation but without any predisposing immunodeficiency. Given the expression of the EBV latent genes, DLBCL-CI should have mechanisms for evasion of host antitumor immunity. EBV-positive pyothorax-associated lymphoma (PAL) is a prototype of DLBCL-CI and may provide a valuable model for the study of immune evasion by DLBCL-CI. This study demonstrates that PAL cell lines express and secrete CCL17 and/or CCL22 chemokines, the ligands of C-C motif chemokine receptor 4 (CCR4), in contrast to EBV-negative DLBCL cell lines. Accordingly, culture supernatants of PAL cell lines efficiently attracted CCR4-positive regulatory T (Treg) cells in human peripheral blood mononuclear cells. PAL cells injected into mice also attracted CCR4-expressing Treg cells. Furthermore, this study confirmed that CCR4-expressing Treg cells were abundantly present in primary PAL tissues. Collectively, these findings provide new insight into the mechanisms of immune evasion by PAL, and further studies are warranted on whether such mechanisms eventually lead to the development of DLBCL-CI.
EBV 阳性弥漫性大 B 细胞淋巴瘤伴慢性炎症（DLBCL-CI）发生于慢性炎症患者，但不存在任何易患免疫缺陷。鉴于 EBV 潜伏基因的表达，DLBCL-CI 应该具有逃避宿主抗肿瘤免疫的机制。EBV 阳性脓胸相关淋巴瘤（PAL）是 DLBCL-CI 的典型代表，可能为研究 DLBCL-CI 的免疫逃避提供有价值的模型。本研究表明，PAL 细胞系表达和分泌 CCL17 和/或 CCL22 趋化因子，即 C 型趋化因子受体 4（CCR4）的配体，而 EBV 阴性 DLBCL 细胞系则不表达。因此，PAL 细胞系的培养上清液可有效吸引人外周血单个核细胞中 CCR4 阳性调节性 T（Treg）细胞。将 PAL 细胞注入小鼠体内也可吸引 CCR4 表达的 Treg 细胞。此外，本研究还证实 CCR4 表达的 Treg 细胞在原发性 PAL 组织中大量存在。综上所述，这些发现为 PAL 的免疫逃避机制提供了新的见解，需要进一步研究这些机制是否最终导致 DLBCL-CI 的发生。
