Clinicopathological significance of peritumoral alveolar macrophages in patients with resected early-stage lung squamous cell carcinoma
Clinicopathological significance of peritumoral alveolar macrophages in patients with resected early-stage lung squamous cell carcinoma
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DOI：
10.1007/s00262-023-03393-8
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发表时间：
2023-03
期刊：
影响因子：
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通讯作者：
Yu Tanaka;T. Nakai;A. Suzuki;Yosuke Kagawa;Osamu Noritake;T. Taki;H. Hashimoto;T. Sakai;Y. Shibata;H. Izumi;K. Nosaki;H. Udagawa;Y. Zenke;S. Matsumoto;K. Yoh;Saori Miyazaki;Naoya Sakamoto;Shingo Sakashita;M. Kojima;Reiko Watanbe;M. Tsuboi;K. Goto;G. Ishii
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文献类型：
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作者：
Yu Tanaka;T. Nakai;A. Suzuki;Yosuke Kagawa;Osamu Noritake;T. Taki;H. Hashimoto;T. Sakai;Y. Shibata;H. Izumi;K. Nosaki;H. Udagawa;Y. Zenke;S. Matsumoto;K. Yoh;Saori Miyazaki;Naoya Sakamoto;Shingo Sakashita;M. Kojima;Reiko Watanbe;M. Tsuboi;K. Goto;G. Ishii
研究方法：我们回顾了我院124例I期肺SqCC病例和139例I期肺38例SqCC病例的癌症基因组图谱（TCGA）队列研究。我们在瘤周肺野（P-AM）中计数了39个AM，在远离肿瘤的肺野（D-AM）中计数了40个。此外，我们进行了一种新的离体支气管肺泡灌洗液（BALF）分析，以选择来自手术切除的肺SqCC病例的AM，并检测了42例中IL 10、CCL 2、IL 6、TGFβ和TNFα的表达（n= 3）。43个结果：具有高P-AM的患者具有显著较短的总生存期（OS）44（p< 0.01）;然而，具有高D-AM的患者没有显著较短的OS 45。此外，在TCGA队列中，具有高P-AM的患者具有显著较短的OS 46（p< 0.01）。在多变量分析中，较高数量的P-AM是独立的不良预后因素（p= 0.02）。离体BALF分析显示，在所有3例病例中，从48个肿瘤附近收集的AM显示出比从远处肺49个野收集的AM更高的IL-10和CCL 2表达（IL-10：2.2、3.0和10.0倍; CCL-2：3.0、3.1和3.2倍）。此外，添加重组CCL 2显著增加了51
Methods: We reviewed 124 stage I lung SqCC cases in our hospital and 139 stage I lung 38 SqCC cases in The Cancer Genome Atlas (TCGA) cohort in this study. We counted the 39 number of AMs in the peritumoral lung field (P-AMs), and in the lung field distant from 40 the tumor (D-AMs). Moreover, we performed a novel ex vivo bronchoalveolar lavage 41 fluid (BALF) analysis to select AMs from surgically resected lung SqCC cases and 42 examined the expression of IL10, CCL2, IL6, TGFβ, and TNFα (n= 3). 43 Results: Patients with high P-AMs had significantly shorter overall survival (OS) 44 (p< 0.01); however, patients with high D-AMs did not have significantly shorter OS. 45 Moreover, in TCGA cohort, patients with high P-AMs had a significantly shorter OS 46 (p< 0.01). In multivariate analysis, a higher number of P-AMs was an independent poor 47 prognostic factor (p= 0.02). Ex vivo BALF analysis revealed that AMs collected from the 48 tumor vicinity showed higher expression of IL10 and CCL2 than AMs from distant lung 49 fields in all 3 cases (IL-10: 2.2, 3.0, and 10.0-fold; CCL-2: 3.0, 3.1, and 3.2-fold). 50 Moreover, the addition of recombinant CCL2 significantly increased the proliferation of 51