CCR9在非小细胞肺癌患者外周血CD4^+T淋巴细胞中的表达及其对趋化活性的影响

Expression of CCR9 on peripheral blood CD4^+T lymphocytes in non-small cell lung cancer patients and its chemotactic activity

目的探讨CC族趋化因子受体9(CCR9)在非小细胞肺癌(NSCLC)肿瘤免疫机制中的作用。方法采用流式细胞术检测42例NSCLC患者和30名健康人手术前后T细胞亚群以及外周血中CD4+T淋巴细胞表面CCR9的表达情况,计数各组细胞表达的百分率。免疫磁珠分选外周血CD4+T淋巴细胞,采用transwell实验检测并分析CCL25/CCR9对CD4+T淋巴细胞迁移的影响。结果 NSCLC患者外周血T淋巴细胞亚群均降低,术后外周血CD4+T淋巴细胞、CD4+/CD8+比值均明显高于术前[(49.11±8.32)vs(46.17±8.71),P=0.031和(1.66±0.09)vs(1.44±0.06),P=0.001];术前CD4+CCR9+T淋巴细胞的百分率低于术后[(3.33±1.11)vs(6.57±1.92),P<0.05]和健康对照组[(3.33±1.11)vs(11.06±1.37),P<0.05]。在CCL25诱导下,NSCLC患者外周血CD4+T淋巴细胞趋化指数(CI)为3.14,明显低于健康对照组的3.83(P<0.05)。经过anti-CCR9单抗处理后,CD4+T淋巴细胞的CI为0.62,与未经anti-CCR9 mAb处理者相比明显降低(P<0.05)。结论 NSCLC患者外周血T淋巴细胞调节机制紊乱,CL25/CCR9相互作用可介导外周血CD4+T淋巴细胞迁移,NSCLC患者外周血淋巴细胞中CCR9低表达,影响淋巴细胞迁移,可能与肿瘤逃避免疫监视的机制有关。手术可以逆转CD4+T淋巴细胞表面CCR9的表达变化,CCR9可能作为评价肺癌治疗后免疫重建的指标。

Objective To investigate the expression of CC chemokine receptor 9 （ CCR9 ） on peripheral blood CD4 ＋T lymphocyte cells of non small cell lung cancer （ NSCLC）, and the effect of CCR9 and its ligand （CCL25） on peripheral blood CD4＋T lymphocytes.Methods The study was performed in 42 NSCLC patients and 30 healthy controls .Flow cytometry was employed to detect the T lymphocyte subsets and the expression of CCR 9 on peripheral blood CD4 ＋T cells.Peripheral blood CD4 ＋T lymphocytes were isolated from all cases with magnetic-acti-vated cell sorting method .The cell trans-membrane test with 24-transwell was used to detect the effect of CCR 9/CCL25 on the lymphocyte migration .Results Compared with control group , the T lymphocyte subsets in pre-opera-tive patients were higher than that in post-operative patients（P〈0.05）.The frequency of CD4 ＋CCR9＋T lympho-cyte in pre-operative group was both significantly decreased compared with post-operative group（3.33 ±1.11 vs 6.57 ± 1.92,P〈0.05） and controls（3.33 ±1.11 vs 11.06 ±1.37,P〈0.05）.In the induce of CCL25, the chemotactic indexes（CI） of CD4 ＋T lymphocytes from NSCLC patients （3.14） was significantly lower than that from healthy per-sons（3.83）.After anti-CCR9 mAb pretreatment, the lymphocytes CIs of NSCLC patients decreased significantly to＆nbsp;0.62 as compared with untreated controls .Conclusion The expression of CCR9 is down-regulated on NSCLC periph-eral blood CD4＋T lymphocyte cells .CCR9/CCL25 interactions mediate the migration of CD 4 ＋T lymphocytes in bodies .The decreased expression of CCR 9 in the CD4＋T lymphocytes of patients with NSCLC could effect the ability of lymphocytes migration , which might involve in the mechanisms of tumor escape immune surveillance .Operation could reverse the change of CCR 9 expression on CD4 ＋T lymphocyte cells .CCR9 may be suggested to indicate immu-nologic reconstitution after therapy and operation .