• Edwin R Parra, Carmen Behrens, Jaime Rodriguez-Canales, Heather Lin, Barbara Mino, Jorge Blando, Jianjun Zhang, Don L Gibbons, John V Heymach, Boris Sepesi, Stephen G Swisher, Annikka Weissferdt, Neda Kalhor, Julie Izzo, Humam Kadara, Cesar Moran, Jack J Lee, and Ignacio I Wistuba.
• Departments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
• Clin Cancer Res. 2016 Dec 15; 22 (24): 6278-6289.

PurposeWe investigated the correlation between immunohistochemical PD-L1 expression and tumor-associated immune cells (TAICs) density in non-small cell lung carcinoma (NSCLC) and correlated them with clinicopathologic variables.Experimental DesignTumor tissue specimens from 254 stage I-III NSCLCs [146 adenocarcinomas; 108 squamous cell carcinomas (SCCs)] were examined. PD-L1 expression in malignant cells and macrophages and the density of TAICs expressing CD3, CD4, CD8, CD57, granzyme B, CD45RO, PD-1, FOXP3, and CD68 were evaluated using immunohistochemistry and image analysis.ResultsMalignant cells PD-L1 H-score > 5 was detected in 23% of adenocarcinomas and 31% of SCCs, and no significant differences were detected comparing both histologies; the median H-score in macrophages was significantly higher in SCC than in adenocarcinoma (P < 0.001). In adenocarcinoma, high malignant cells PD-L1 expression and high TAIC density correlated with solid histology, smoking history, and airflow limitation. Multivariate analysis demonstrated that high CD57-positive cell density correlated with better recurrence-free survival (RFS; P = 0.0236; HR, 0.457) and overall survival (OS; P = 0.0261; HR, 0.481) rates for SCC. High CD68-positive cell density in intratumoral compartment correlated with better RFS (P = 0.0436; HR, 0.553) for adenocarcinoma. The combination of low CD4/CD8/C68-positive cell density and PD-L1 H-score >5 in malignant cells identified small subset of adenocarcinomas with worse outcomes (RFS: P = 0.036; HR, 4.299; OS: P = 0.00034; HR, 5.632).ConclusionsWe detected different PD-L1 expression and TAIC density patterns in NSCLC. Distinct groups of tumor microenvironment correlated with NSCLC clinicopathologic features, including outcome. Clin Cancer Res; 22(24); 6278-89. ©2016 AACR.©2016 American Association for Cancer Research.

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