Tumor-associated macrophage infiltration is associated with a higher rate of tumor spread through air spaces in resected lung adenocarcinomas
Tumor-associated macrophage infiltration is associated with a higher rate of tumor spread through air spaces in resected lung adenocarcinomas
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在手术切除的肺腺癌中，肿瘤相关巨噬细胞浸润与肿瘤经气腔扩散的较高发生率相关。
DOI：
10.1016/j.lungcan.2021.06.009
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发表时间：
2021-06-15
期刊：
影响因子：
5.3
通讯作者：
Yokomise, Hiroyasu
中科院分区：
文献类型：
--
作者：
Yoshida, Chihiro;Kadota, Kyuichi;Yokomise, Hiroyasu
目的：肺癌可以通过多种方式传播，其中一种被认为是通过空气空间（STAS）传播。肿瘤免疫微环境似乎在这种传播中发挥着重要作用。特别是，肿瘤相关巨噬细胞（TAM）可以为肿瘤进展创造有利的微环境。在这项研究中，我们分析了 1999 年至 2016 年间切除的 709 例 0-IIIA 期肺腺癌患者的数据，并研究了免疫细胞浸润是否与 STAS 的发生和该疾病的临床结果相关。材料和方法：构建组织微阵列，并对CD3、CD4、CD8、CD45RO、CD25、CD20和CD68进行免疫组织化学分析。对免疫细胞密度最高的三个肿瘤区域进行拍照，并对免疫细胞进行定量。使用卡方检验和曼-惠特尼 U 检验分析变量之间的关联。使用对数秩检验和 Cox 比例风险模型分析无复发概率和总生存率。结果：在分析 STAS 与每种类型的免疫细胞浸润之间的关联后，高密度 CD68 + TAM 被确定为高 STAS 率的独立预测因子 (p = 0.014)，并且使用单变量分析发现与高复发风险相关 (p = 0.008)。在调整 CD68+ TAM、病理分期和淋巴管侵犯后，STAS 仍然与高复发风险显着相关（HR = 3.50，p < 0.001）。结论：我们证明高密度的 CD68 + TAM 是 STAS 率增加的独立预测因子。此外，STAS 与侵袭性肿瘤行为特征相关。
Objective: Lung cancer can spread in numerous ways, one of which has been suggested to be spread through air spaces (STAS). The tumor immune microenvironment appears to play a significant role in this spread. Particularly, tumor-associated macrophages (TAMs) can create a favorable microenvironment for tumor progression. In this study, we analyzed data from 709 patients with stage 0-IIIA lung adenocarcinoma, resected between 1999 and 2016, and investigated whether immune cell infiltration was associated with the occurrence of STAS and clinical outcome of the disease. Materials and methods: Tissue microarrays were constructed, and immunohistochemical analysis was performed for CD3, CD4, CD8, CD45RO, CD25, CD20, and CD68. The three tumor areas with the highest density of immune cells were photographed, and the immune cells were quantified. Associations between variables were analyzed using chi-square tests and Mann-Whitney U tests. Recurrence-free probability and overall survival were analyzed using log-rank tests and Cox proportional hazards models. Results: After analyzing the associations between STAS and each type of immune cell infiltration, high density of CD68 + TAMs was identified as an independent predictor of a high STAS rate (p = 0.014) and was found to be associated with a high risk of recurrence, using univariate analysis (p = 0.008). After adjusting for CD68+ TAMs, pathological stage, and lymphovascular invasion, STAS remained significantly associated with a high risk of recurrence (HR = 3.50, p < 0.001). Conclusion: We demonstrated that a high density of CD68 + TAMs is an independent predictor of an increased STAS rate. Additionally, STAS is correlated with aggressive tumor behavior characteristics.