TY - JOUR
T1 - Image analysis-based assessment of PD-L1 and tumor-associated immune cells density supports distinct intratumoral microenvironment groups in non-small cell lung carcinoma patients
AU - Parra, Edwin R.
AU - Behrens, Carmen
AU - Rodriguez-Canales, Jaime
AU - Lin, Heather
AU - Mino, Barbara
AU - Blando, Jorge
AU - Zhang, Jianjun
AU - Gibbons, Don L.
AU - Heymach, John V.
AU - Sepesi, Boris
AU - Swisher, Stephen G.
AU - Weissferdt, Annikka
AU - Kalhor, Neda
AU - Izzo, Julie
AU - Kadara, Humam
AU - Moran, Cesar
AU - Lee, Jack J.
AU - Wistuba, Ignacio I.
N1 - Publisher Copyright:
©2016 AACR.
PY - 2016/12/15
Y1 - 2016/12/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85007001788&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85007001788&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-15-2443
DO - 10.1158/1078-0432.CCR-15-2443
M3 - Article
C2 - 27252415
AN - SCOPUS:85007001788
SN - 1078-0432
VL - 22
SP - 6278
EP - 6289
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 24
ER -