目的：探讨CD68+ 肿瘤相关巨噬细胞（TAM）、CD8+ T 细胞、Foxp3+ Treg 细胞等在肺腺癌（LUAD）组织中浸润分布及 其与患者预后的关系。方法：收集2004 年9 月至2009 年4 月间在苏州大学附属第三医院手术切除的93 例LUAD 组织及78 例癌 旁组织，采用组织芯片（TMA）及多重免疫荧光（mIF）技术检测其中的免疫细胞浸润与分布，Wilcoxon 秩和检验比较癌与癌旁组 织、癌巢与间质中浸润水平的差异，χ2 检验分析其浸润水平及CD8+/CD68+细胞比值与临床病理特征的关系，Kaplan-Meier 法和 COX 模型分析影响患者OS 的潜在危险因素。结果：与癌旁组织比较，癌组织中CD68+ TAM、CD8+ T 细胞、Foxp3+ Treg 细胞浸润 水平均显著增加（均P<0.01），间质CD68+ TAM、CD8+ T 细胞的浸润水平均显著高于癌巢（均P<0.01）。总CD68+ TAM、癌巢及间质 CD68+ TAM 浸润水平与淋巴结转移呈正向关联（均P<0.05），癌巢CD68+ TAM 浸润水平与T 分期呈正向关联（P<0.05），间质 CD68+ TAM 浸润水平与病理分级呈正向关联（P<0.05）；癌组织中CD8+/CD68+细胞比值与病理分级、淋巴结转移均呈负向关联（均 P<0.05）。Kaplan-Meier 生存分析显示，LUAD 组织中总CD68+ TAM、癌巢及间质CD68+ TAM 高浸润患者OS 均短于低浸润患者（P<0.05 或P<0.01）、癌组织中CD8+/CD68+细胞比值高患者OS 显著长于低比值患者（P<0.05）。多因素COX 模型分析示，LUAD 患者年龄、TNM 分期及癌组织中CD8+/CD68+ 细胞比值是影响患者预后的独立风险因素（P<0.05或P<0.01）。结论:高度浸润的 CD68+TAM与LUAD的进展、侵袭、转移和不良预后显著关联，而高CD8+/CD68+ 细胞比值是影响LUAD 患者OS 的独立保护因素。

Objective: To investigate the distribution of CD68+ tumor-associated macrophages (TAM), CD8+ T cells, Foxp3+ Treg cells, and other immune cells infiltrating lung adenocarcinoma (LUAD) tissues and their associations with patient prognosis. Methods: Ninety-three cases of LUAD tissues and 78 cases of paraneoplastic tissues surgically resected at the Third Affiliated Hospital of Soochow University between September 2004 and April 2009 were collected. The immune cell infiltration and distribution were detected by tissue microarray (TMA) and multiplex immunofluorescence (mIF) techniques. The Wilcoxon rank sum test was used to compare the differences in infiltration levels between cancer and paraneoplastic tissues, and between cancer nests and interstitial tissues. χ2 test was employed to analyze the relationship between their infiltration levels, CD8+/CD68+ cell ratios and clinicopathological features. Kaplan-Meier method and COX model were used to analyze the potential risk factors affecting patients' OS. Results: The infiltration levels of CD68+ TAM, CD8+ T cells, and Foxp3+ Treg cells in cancer tissues were significantly higher than those in paraneoplastic tissues (all P<0.01) while the infiltration levels of CD68+ TAM and CD8+ T cells in the interstitial tissues were significantly higher than that in the cancer nests (all P<0.01). The levels of total CD68+ TAM, cancer nest and interstitial CD68+ TAM infiltration were positively correlated with lymph node metastasis (all P<0.05); the levels of CD68+ TAM infiltration in cancer nests were positively correlated with T stage (P<0.05), and the levels of interstitial CD68+ TAM infiltration were positively correlated with pathological grading (P<0.05); the CD8+/CD68+ cell ratio in cancer tissues was negatively correlated with pathological grading and lymph node metastasis (all P<0.05). Kaplan-Meier survival analysis showed that the OS of patients with high infiltration of total CD68+ TAM, cancer nests and interstitial CD68+ TAM in LUAD tissues was shorter than that of patients with low infiltration (P<0.05 or P<0.01), and the OS of patients with high CD8+/CD68+ cell ratio in cancer tissues was significantly longer than that of patients with low ratio (P<0.05). Multivariate COX model analysis showed that age, TNM stage and CD8+/CD68+ cell ratio in cancer tissues were independent risk factors for the prognosis of LUAD patients (P<0.05 or P<0.01). Conclusion: Highly infiltrative CD68+ TAM was significantly associated with the progression, invasion, metastasis and poor prognosis of LUAD, and a high CD8+/CD68+ cell ratio was an independent protective factor for the OS of patients with LUAD.

江苏省“六个一”拔尖人才资助项目（No. LGY2020034）；常州市卫生拔尖人才资助项目（No. 2016CZBJ018）：常州市应用基础研究计划资助 项目（No. CJ20210089）；常州市国际合作资助项目（No. CZ20210035）