Tumor Cd47 Expression And A High M2/M1 Ratio Of Tumor-Associated Macrophages As An Adverse Prognostic Factor In Resected Stage. A Non-Small Cell Lung Cancer.

Journal of Clinical Oncology(2018)

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摘要
e20531 Background: Immunotherapy is one of the most promising advances in the field of oncology. However, limited information exists regarding characterization of the tumor associated macrophages (TAMs) related immune microenvironment in patients with non-small cell lung cancer (NSCLC), by which it may possible to predict the efficacy of novel immunotherapies. Methods: 191 resected NSCLC specimens were retrospectively studied for the expression of CD47 expression was examined using immunohistochemistry (IHC). The infiltration of TAMs (M2-macrophages & M1-macrophages) and PD-L1 expression& CD8+T-lymphocytes were evaluated using dual-IF staining, respectively. 47 cases of pulmonary infectious diseases served as the control group. Finally, the prognostic role of these immune features was assessed in stage IIIa NSCLC. Results: CD47-positive staining was observed in 53.4% (102/191) of NSCLC and 78.7% (37/47) of pulmonary infectious samples, respectively (P = 0.002). CD47 expression was more frequently detected in adenocarcinoma, female, never-smoking, stage Ⅲa, and high-differentiation NSCLCs (P < 0.001, P = 0.002, 0.008, 0.035 and 0.001, respectively). 65.3% (62/95) of Stage Ⅲa cases detected M2-macrophage infiltration in tumor area, significantly higher compared to 32.3% (31/96) of Stage Ⅰ (P < 0.001) . A high M2 / M1 ratio was more common in NSCLC compared with the control group (71.7% vs 46.8%, P = 0.001), especially in stage Ⅲa NSCLC (stage Ⅰ vs stage Ⅲa: 60.4% vs 84.2%, P < 0.001). Patients expressing CD47 or with concurrence of CD47+ and high M2/M1 ratio tended to show poor DFS (22.03 ms vs 34.77 ms, P = 0.021; 19.97ms vs 34.77ms, P = 0.005), and multivariate analysis identified the latter one as negative predictor for DFS (P = 0.016). Conclusions: Tumor CD47 expression and a high M2/M1 ratio of tumor-associated macrophages is an adverse prognostic factor in resected stage Ⅲa NSCLC. Anti-CD47 treatment might be a novel adjuvant treatment option for resected stage Ⅲa NSCLC.
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关键词
lung cancer,macrophages,tumor-associated,non-small
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