Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Respiratory Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Immunology. 2020 Jun;160(2):209-219. doi: 10.1111/imm.13189. Epub 2020 Apr 7.
CD100 is an immune semaphorin constitutively expressed on T-cells. Matrix metalloproteinase (MMP) is an important mediator of membrane-bound CD100 (mCD100) cleavage to generate soluble CD100 (sCD100), which has immunoregulatory activity in immune cell responses. The aim of the study was to investigate the level and role of sCD100 and mCD100 in modulating CD8 T-cell function in non-small cell lung cancer (NSCLC). sCD100 and MMP-14 levels in the serum and bronchoalveolar lavage fluid (BALF), and mCD100 expression on peripheral and lung-resident CD8 T-cells were analysed in NSCLC patients. The ability to induce sCD100 and the effect of MMP-14 on mCD100 shedding for the regulation of non-cytolytic and cytolytic functions of CD8 T-cells were also analysed in direct and indirect contact co-culture systems. NSCLC patients had lower serum sCD100 and higher mCD100 levels on CD8 T-cells compared with healthy controls. BALF from the tumour site also had decreased sCD100 and increased mCD100 on CD8 T-cells compared with the non-tumour site. Recombinant CD100 stimulation enhanced non-cytolytic and cytolytic functions of CD8 T-cells from NSCLC patients, whereas blockade of CD100 receptor CD72 attenuated CD8 T-cell activity. NSCLC patients had lower MMP-14 in the serum and in BALF from the tumour site. Recombinant MMP-14 mediated mCD100 shedding from CD8 T-cell membrane, and led to promotion of CD8 T-cell response in NSCLC patients. Overall, decreased MMP-14 resulted in insufficient CD100 shedding, leading to suppression of peripheral and lung-resident CD8 T-cell activity in NSCLC.
CD100 是一种在 T 细胞上持续表达的免疫信号素。基质金属蛋白酶 (MMP) 是膜结合型 CD100(mCD100) 切割生成可溶性 CD100(sCD100) 的重要介质，后者具有免疫调节活性，可影响免疫细胞反应。本研究旨在探讨 sCD100 和 mCD100 在非小细胞肺癌 (NSCLC) 中调节 CD8 T 细胞功能中的水平和作用。分析 NSCLC 患者血清和支气管肺泡灌洗液 (BALF) 中的 sCD100 和 MMP-14 水平，以及外周血和肺驻留 CD8 T 细胞上的 mCD100 表达。还在直接和间接接触共培养系统中分析了诱导 sCD100 的能力以及 MMP-14 对 mCD100 脱落的影响，以调节 CD8 T 细胞的非细胞溶解和细胞溶解功能。与健康对照者相比，NSCLC 患者的血清 sCD100 水平较低，CD8 T 细胞上的 mCD100 水平较高。与非肿瘤部位相比，肿瘤部位的 BALF 中 CD8 T 细胞上的 sCD100 水平降低，mCD100 水平升高。重组 CD100 刺激增强了 NSCLC 患者 CD8 T 细胞的非细胞溶解和细胞溶解功能，而阻断 CD100 受体 CD72 则减弱了 CD8 T 细胞的活性。NSCLC 患者血清和肿瘤部位 BALF 中的 MMP-14 水平较低。重组 MMP-14 介导 CD8 T 细胞膜上的 mCD100 脱落，并导致 NSCLC 患者 CD8 T 细胞反应增强。总体而言，MMP-14 减少导致 CD100 脱落不足，从而抑制 NSCLC 患者外周血和肺驻留 CD8 T 细胞的活性。
