Journal
CLINICAL CANCER RESEARCH
Volume 22, Issue 24, Pages 6278-6289Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-15-2443
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Funding
- Department of Defense PROSPECT grant [W81XWH-07-1-0306]
- Cancer Prevention Research Institute of Texas Multi-Investigator Research Award [RP120713, RP150405]
- University of Texas Lung Specialized Programs of Research Excellence grant [P50CA70907]
- MD Anderson's Institutional Tissue Bank Award from the National Cancer Institute [2P30CA016672]
- Jeane F. Shelby Scholarship Fund
- Core Grant-NIH Cancer Center Support Grant [CA016672]
- National Counsel of Technological and Scientific Development of the Ministry of Science, Technology and Innovation of Brazil [P246042/2012-5]
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Purpose: We 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 Design: Tumor 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. Results: Malignant 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). Conclusions: We detected different PD-L1 expression and TAIC density patterns in NSCLC. Distinct groups of tumor microenvironment correlated with NSCLC clinicopathologic features, including outcome. (C)2016 AACR.
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