Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
Int J Cancer. 2010 Dec 1;127(11):2598-611. doi: 10.1002/ijc.25281.
Tumor-induced immune suppression involves the accumulation of suppressive infiltrates in the tumor microenvironment such as regulatory T-cells (Tregs). Previous studies demonstrated that NK-dependant increases in CCL22 secretion selectively recruit Tregs toward murine lungs bearing Lewis Lung Carcinoma (LLC). To extend the in vitro studies, the present studies utilized in vivo depletion of NK cells to ascertain the contribution of NK-derived CCL22 toward total CCL22 and subsequent Treg levels in both normal and LLC-bearing lungs. However, NK depletion had the unexpected effect of increasing both CCL22 secretion and Treg levels in the lungs of NK-depleted LLC-bearing mice. This was concurrent with an increase in tumor burden. Flow cytometry and a series of both immunomagnetic and FACS isolations were used to identify the CCL22-producing cellular fractions in LLC-bearing lungs. A novel CD11b(+)CD11c(+) cell population was identified that accumulates in large numbers in NK-depleted LLC-bearing lung tissue. These CD11b(+)CD11c(+) cells secreted large amounts of CCL22 that may overcompensate for the loss of NK-derived CCL22 in the lungs of NK-depleted LLC-bearing mice. Taken together, these data suggest that NK cells play both a positive and negative role in the regulation of CCL22 secretion and, in turn, the recruitment of Tregs toward LLC-bearing lungs.
肿瘤诱导的免疫抑制涉及抑制性浸润物在肿瘤微环境中的积累，如调节性 T 细胞（Tregs）。先前的研究表明，NK 细胞依赖性 CCL22 分泌的增加选择性地将 Tregs 招募到携带 Lewis 肺癌（LLC）的小鼠肺部。为了扩展体外研究，本研究利用体内 NK 细胞耗竭来确定 NK 衍生的 CCL22 对正常和携带 LLC 的肺部中总 CCL22 和随后的 Treg 水平的贡献。然而，NK 细胞耗竭出人意料地增加了 NK 细胞耗竭的携带 LLC 的小鼠肺部中的 CCL22 分泌和 Treg 水平。这与肿瘤负担的增加同时发生。流式细胞术和一系列免疫磁珠和 FACS 分离用于鉴定携带 LLC 的肺部中产生 CCL22 的细胞分数。鉴定出一种新型的 CD11b(+)CD11c(+)细胞群体，其在 NK 细胞耗竭的携带 LLC 的肺部组织中大量积累。这些 CD11b(+)CD11c(+)细胞分泌大量的 CCL22，可能弥补 NK 细胞耗竭的携带 LLC 的小鼠肺部中 NK 衍生的 CCL22 的损失。总之，这些数据表明 NK 细胞在 CCL22 分泌的调节以及随后 Tregs 向携带 LLC 的肺部的募集中发挥着积极和消极的作用。
