1 青岛大学附属青岛市市立医院，山东 青岛 266000
2 青岛市市立医院病理科，山东 青岛 266000
3 青岛市市立医院呼吸与危重症医学二科，山东 青岛 266000
|| 山东省卫健委课题 (2017wj309)。
目的：通过评估CD68和CD206在肿瘤间质及癌巢中的表达，探讨M2型肿瘤相关巨噬细胞在非小细胞肺癌(non-small cell lung cancer，NSCLC)中的作用及临床意义。方法：收集115例NSCLC标本，通过免疫组织化学染色检测CD68、CD206的表达并计算其数量，分析不同部位的M2型肿瘤相关巨噬细胞与肿瘤临床特征的相关性；同时结合肿瘤EGFR基因突变检测，分析M2型肿瘤相关巨噬细胞与基因突变状态的相关性。结果：癌巢和间质内CD68和CD206的表达均高于周围正常组织，且在肿瘤间质内的表达显著高于癌巢。癌巢内CD68与肿瘤大小、TNM分期呈负相关，肿瘤间质内CD68与肿瘤远处转移呈负相关。癌巢CD206的表达在女性患者中显著高于男性患者，且与肿瘤大小及分期呈负相关；肿瘤间质中CD206的表达在男性患者中显著高于女性患者，且与肿瘤大小呈正相关。女性NSCLC患者癌巢的CD206与肿瘤大小、临床分期及远处转移呈负相关。腺癌中癌巢与间质CD206与肿瘤进展呈负相关。男性患者癌巢CD206的表达与EGFR突变相关。结论：M2型肿瘤相关巨噬细胞的数量与NSCLC的肿瘤进展密切相关，其在不同的组织学类型、不同性别及肿瘤不同位置中对肿瘤的发生发展作用具有差异性，该研究结果为以M2型肿瘤细胞为靶点的靶向药物的研发提供新的证据及思路。
Effects and clinical significance of M2 tumor-associated macrophages in non-small cell lung cancer
CorrespondingAuthor: HUANG Weiqing
This work was supported by Shandong Provincial Health Commission, China (2017wj309).
Objective: To explore the effects and clinical significance of M2 tumor-associated macrophages in non-small cell lung cancer (NSCLC) through evaluating the expressions of CD68 and CD206 in tumor stroma and cancer nests. Methods: A total of 115 NSCLC specimens were collected. Immunohistochemical staining was performed to detect the expression and calculate the number of CD68 and CD206. The correlation between M2 tumor-associated macrophages and tumor clinicopathological features at different locations was analyzed. At the same time, the correlation between M2 tumor-associated macrophages and gene mutation status was also analyzed in combination with EGFR gene mutation detection. Results: The expressions of CD68 and CD206 were higher in both cancer nests and tumor stroma than those in the corresponding normal tissues. The expressions in tumor stroma were significantly higher than those in cancer nests. CD68 expressions in cancer nests was negatively correlated with tumor size and TNM stage. CD68 in tumor stroma was negatively correlated with distant metastasis of tumors. The expression of CD206 in cancer nests was significantly higher in female patients than that in male patients, and was negatively correlated with tumor size and stage. The expression of CD206 in tumor stroma was significantly higher in male patients than that in female patients and positively correlated with tumor size. In female NSCLC patients, CD206 in cancer nests was negatively correlated with tumor size, TNM stage and distant metastasis. The expressions of CD206 in adenocarcinoma were negatively associated with tumor development. The expressions of CD206 in tumor nests were associated with EGFR mutations in male but not in female. Conclusion: The number of M2 tumor-associated macrophages is closely related to the tumor progression of NSCLC. M2 tumor-associated macrophages have different effects on the initiation and development of NSCLC tumors in different histological types, different genders, and different locations of the tumor. The results of this study provide new evidence and ideas for the development of therapeutic drugs targeting M2 tumor cells.
non-small cell lung cancer; tumor inflammatory microenvironment; tumor-associated macrophages