非小细胞肺癌肿瘤微环境中NK细胞和TAMs的分布特点

Distribution of NK cells and TAMs in tumor microenvironments of non-small cell lung cancer

目的探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)肿瘤微环境(tumor microenvironment,TME)中自然杀伤(natural killer,NK)细胞和肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)的分布特点及其临床意义。方法收集87例空军特色医学中心(原空军总医院)2016年1月—2018年6月NSCLC的患者术后临床资料,分析肿瘤组织中CD56、CD68和CD163表达情况,并对患者进行定期随访。结果87例患者中,CD56~+NK细胞阳性表达27例(31.03%),阴性表达60例(68.97%);Ⅲ期、EGFR野生型的NSCLC组织中CD56~+NK的阳性率高,差异有统计学意义(P<0.05),边缘型和中心型CD68~+TAMs在Ⅲ期的NSCLC组织较Ⅰ-Ⅱ期浸润程度高(P<0.05)。边缘型CD163~+TAMs在Ⅲ期、腺癌的NSCLC患者组织中高于Ⅰ-Ⅱ期、鳞癌的浸润(P<0.05);中心型CD163~+TAMs在吸烟、腺癌、Ⅲ期、EGFR野生型NSCLC患者组织中高浸润(P<0.05)。截止随访终点,复发44例,中位无病生存期(disease free survival,DFS)43.0个月。经Log-rank分析,边缘型CD68~+TAMs和边缘型CD163~+TAMs高浸润的NSCLC患者DFS较短;多因素分析边缘型CD163~+TAMs高浸润是DFS的影响因素。结论NSCLC患者肿瘤组织中边缘型CD68~+TAMs和边缘型CD163~+TAMs高浸润是影响DFS的独立危险因素。CD163~+TAMs较CD68~+TAMs更适合定义具有免疫抑制性TME。

Objective To investigate the distribution of natural killer(NK)cells and tumor associated macrophages(TAMs)in a tumor microenvironment(TME)of non-small cell lung cancer(NSCLC).Methods The clinical data of 87 patients with NSCLC,including expressions of CD56、CD68 and CD163 in tumor tissues,was analyzed and followed up between January 2016 and June 2018.Results The positive rate of CD56+NK cells in NSCLC tissues was 31.03%(27 cases)and the negative rate was 68.97%(60 cases).The positive rate of CD56+NK was higher in stageⅢand EGFR wild-type NSCLC tissues(P<0.05).Stromal and islet CD68+TAMs were more highly infiltrated in stageⅢNSCLC tissues than in stageⅠ-Ⅱ(P<0.05).The infiltration of stromal CD163+TAMs in the tissues of NSCLC patients in stageⅢor with adenocarcinoma was higher than in stageⅠ-Ⅱ,squamous cell carcinoma(P<0.05).The high infiltration of islet CD163+TAMs was enriched in the tissues of NSCLC patients with a history of smoking or adenocarcinoma or in stageⅢor of the EGFR wild type(P<0.05).At the end of follow-up,recurrence was found in 44 cases,and the median disease free survival(disease free survival,DFS)was 43.0 months.Log-rank analysis suggested that the DFS of NSCLC patients with stromal CD68+TAMs and stromal CD163+TAMs high infiltration was shorter.Multivariate analysis confirmed that higher infiltration of CD163+TAMs in tumor stroma was an independent prognostic predictor of deterioration.Conclusion High infiltration of stroma CD68+TAMs and CD163+TAMs in NSCLC is a risk factor for recurrence.CD163+TAM can be more accurately defined as immunosuppressive TME than CD68+TAMs can.