Yoshida Chihiro, Kadota Kyuichi, Yamada Kaede, Fujimoto Syusuke, Ibuki Emi, Ishikawa Ryo, Haba Reiji, Yokomise Hiroyasu
Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Department of Pathology, Faculty of Medicine, Shimane University, Shimane, Japan.
Lung Cancer. 2022 May;167:34-40. doi: 10.1016/j.lungcan.2022.03.016. Epub 2022 Mar 22.
Lung cancer can spread in numerous ways, including spread through air spaces (STAS). A high number of CD68 tumor-associated macrophages (TAMs), which creates a favorable microenvironment for tumor progression, is an independent predictor of increased STAS rate and is used as a pan-macrophage marker, whereas CD163 is used as an M2 macrophage marker. A high number of CD25 tumor-infiltrating lymphocytes (TILs) is associated with the frequency of STAS. This study investigated the influence of M2 macrophages and CD25 TILs on STAS and postoperative recurrence in patients with stage I lung adenocarcinoma who underwent curative resection.
We analyzed data from 485 patients with stage 0-I lung adenocarcinoma who underwent resection between 1999 and 2016. Tissue microarrays were constructed, and immunohistochemical analysis was performed for CD3, CD4, CD8, CD45RO, CD25, CD20, CD68, and CD163. 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 (RFP) was analyzed using log-rank tests and Cox proportional hazards models.
CD163 TAMs were identified as an independent predictor of a higher rate of STAS (P < 0.001). Analysis of biologically relevant immune cell combinations revealed that patients with high CD25 TILs and high CD163 TAMs had a significantly lower RFP (5-year RFP, 74%) than those with other combinations of CD25 and CD163 (5-year RFP, 90%; P < 0.001). Multivariate analysis showed that high CD25/high CD163 immune cell infiltration was an independent predictor of RFP.
We demonstrated that a higher density of M2 macrophages is an independent predictor of a higher STAS incidence. A high CD25/high CD163 immune cell infiltration ratio is a significant prognostic factor for stage 0-I lung adenocarcinoma.
肺癌可通过多种方式扩散，包括气腔播散（STAS）。大量的CD68肿瘤相关巨噬细胞（TAM）为肿瘤进展创造了有利的微环境，是STAS发生率增加的独立预测因子，且用作全巨噬细胞标志物，而CD163用作M2巨噬细胞标志物。大量的CD25肿瘤浸润淋巴细胞（TIL）与STAS的频率相关。本研究调查了M2巨噬细胞和CD25 TIL对接受根治性切除的I期肺腺癌患者STAS及术后复发的影响。
我们分析了1999年至2016年间接受切除的485例0-I期肺腺癌患者的数据。构建组织芯片，并对CD3、CD4、CD8、CD45RO、CD25、CD20、CD68和CD163进行免疫组化分析。拍摄免疫细胞密度最高的三个肿瘤区域，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生存概率（RFP）。
CD163 TAM被确定为STAS发生率较高的独立预测因子（P < 0.001）。对生物学相关免疫细胞组合的分析显示，CD25 TIL高且CD163 TAM高的患者的RFP（5年RFP，74%）显著低于CD25和CD163其他组合的患者（5年RFP，90%；P < 0.001）。多变量分析显示，高CD25/高CD163免疫细胞浸润是RFP的独立预测因子。
我们证明M2巨噬细胞密度较高是STAS发生率较高的独立预测因子。高CD25/高CD163免疫细胞浸润率是0-I期肺腺癌的重要预后因素。
