口腔鳞癌患者外周血单核细胞型髓系抑制细胞的变化及临床意义

Changes and Clinical Significance of Monocytic Myeloid Derived Suppressor Cells in Peripheral Blood of Patients with Oral Squamous Cell Carcinoma

【目的】评价口腔鳞癌(OSCC)患者外周血中髓系抑制细胞(MDSC)变化及与临床意义。【方法】收集2012年1月至2012年10月间在中山大学附属第一医院口腔颌面外科住院的58例口腔鳞癌患者(OSCC组)及20例健康志愿者(对照组)外周血标本,采用流式细胞分析术检测对照组和OSCC组术前外周血中MDSC的表型及比例,比较分析20例口腔鳞癌患者术后3天、7天、30天外周血中MDSC的动态变化;分选CD11b+CD33highHLA-DR-细胞,采用T淋巴细胞增殖实验、精氨酸酶活性检测,以及一氧化氮含量检测验证该群细胞功能;检测血清IL-6含量及与外周血CD11b+CD33highHLA-DR-MDSC变化的相关性。【结果】(1)OSCC组与对照组外周血中CD11b+CD33highHLA-DR-细胞百分率分别为(2.68±0.21)%和(0.65±0.05)%,OSCC组明显高于对照组,两组比较差异具有统计学意义(P<0.001)。(2)口腔鳞癌患者外周血中CD11b+CD33highHLA-DR-细胞是一群CD14+CD15-的有免疫抑制功能单核细胞型髓系抑制细胞(M-MDSC),可抑制T淋巴细胞增殖。(3)M-MDSC的变化与患者临床分期有关,临床Ⅲ、Ⅳ期口腔鳞癌患者与临床Ⅰ、Ⅱ期患者外周血M-MDSC比例分别为(3.01±0.35)%和(2.19±0.19)%,前者明显高于后者,差异具有统计学意义(P<0.05),但M-MDSC的变化与患者年龄、性别、淋巴结转移及病理分级无明显相关性,差异无明显统计学意义(P<0.05)。(4)术后患者外周血中M-MDSC比例在术后3天内明显升高(7.46±0.57)%,7天后逐渐下降(2.56±0.20)%,至术后30天可逐渐下降接近健康者水平(1.07±0.06)%,各组间比较差异有统计学意义(P<0.001)。(5)患者外周血中M-MDSC变化与IL-6含量呈正相关性(P<0.001)。【结论】口腔鳞癌患者外周血M-MDSC的变化与口腔鳞癌发生发展有一定相关性,针对M-MDSC的治疗可能成为加强肿瘤免疫治疗疗效的有效途径。

[ Objective ] To evaluate the changes and clinical significance of myeloid derived suppressor cells （MDSC） in peripheral blood of the patients with oral squamous cell carcinoma （OSCC）. [Methods] From January 2012 to October 2012, 58 OSCC patients and 20 healthy donors were enrolled. The peripheral blood were collected in preoperation. And 20 cases among OSCC patients were also detected at 3 days, 7 days, and 30 days after operation. MDSC phenotype and scale changes were analyzed by flow cytometry. CD1 lbCD33hHLA-DR- MDSC sorting was followed by T cell proliferation experiment, argininase activity and nitric oxide detection. The correlation between I1-6 level and the changes of CD1 lbCD33ShHLA-DR- MDSC in peripheral blood was also detected. [ Results] （1） A significant elevation of CD1 lbCD33HLA-DR- MDSC was observed in the peripheral blood of OSCC patients （2.68 ± 0.21）% compared with healthy donors （0.65 ± 0.05）% （P 〈 0.001）. （2） CDllbCD33HLA-DR- cells was a group of CD14 CD 15- monocytie MDSC （M-MDSC） with immunosuppressive function suppressing T cells proliferation. （3） M-MDSC levels of the patients in clinical phase III and IV （3.01 ± 0.35 ）% were significantly higher than those of the patients in phase I and II （2.19 ± 0.19）% （P 〈 0.05）. However, no correlation was observed between the changes of MDSC and age, metastasis of lymph node or pathological grades （P 〈 0.05）. （4） M-MDSC scales in the peripheral blood of the patients significantly increased at 3 days （7.46 ±0.57）% and reduced at 7 days （2.56 ± 0.20）% after operation. At 30 days after operation, M-MDSC reduced close to the level of healthy donors （1.07± 0.06）% （P 〈 0.001 ）. （5） The levels of MDSC ,in OSCC patients correlated with the contents of IL-6 （r=0.54, P 〈 0.001 ）. [Conclusion] The level of M-MDSC in the peripheral blood can predict the progress of oral squamous cell carcinoma. The manipulation of M-MDSC may be a potential strategy in the search of an .effective immunotherapy for OSCC.