Immunohistochemical and Image Analysis-based Study Demonstrate that Several Immune Checkpoints are Co-expressed in Non-Small Cell Lung Carcinoma Tumors.

Immunohistochemical and Image Analysis-based Study Demonstrate that Several Immune Checkpoints are Co-expressed in Non-Small Cell Lung Carcinoma Tumors.

J Thorac Oncol. 2018 Mar 08;:

Authors: Parra ER, Villalobos P, Zhang J, Behrens C, Mino B, Swisher S, Sepesi B, Weissferdt A, Kalhor N, Heymach JV, Moran C, Zhang J, Lee J, Rodriguez-Canales J, Gibbons D, Wistuba II

Abstract
BACKGROUND: The understanding of immune checkpoint molecules' co-expression in non-small cell lung carcinoma (NSCLC) is important to potentially design combinatorial immunotherapy approaches.
MATERIAL AND METHODS: We studied 225 formalin-fixed, paraffin-embedded tumor tissues from stage I-III NSCLCs-142 adenocarcinomas (ADCs) and 83 squamous cell carcinomas (SCCs)-placed in tissue microarrays. Nine immune checkpoint markers were evaluated; 4 (PD-L1, B7-H3, B7-H4, and IDO-1) expressed predominantly in malignant cells (MCs) and 5 (ICOS, VISTA, TIM3, LAG3, and OX40) expressed mostly in stromal tumor-associated inflammatory cells (TAICs). All markers were examined using a quantitative image analysis and correlated with clinicopathological features, TAICs, and molecular characteristics.
RESULTS: Using above the median value as positive expression in MCs and high density of TAICs expressing those markers, we identified higher expression of immune checkpoints in SCC than ADC. Common simultaneous expression by MCs was PD-L1 + B7-H3 + IDO-1 in ADC and PD-L1 + B7-H3, or B7-H3 + B7-H4, in SCC. TAICs expressing checkpoint were significantly higher in current-smokers than in never-smokers. Almost all the immune checkpoint markers showed positive correlation with TAICs expressing inflammatory cell markers. KRAS-mutant ADC specimens showed higher expression of PD-L1 in MCs and of B7-H3, TIM3, and IDO-1 in TAICs than WT. Kaplan-Meier survival curves showed worse prognosis in ADC patients with higher B7-H4 expression by MCs.
CONCLUSIONS: We found frequent immunohistochemical co-expression of immune checkpoints in surgically resected NSCLC tumors and correlated with tumor histology, smoking history, tumor size, and the density of inflammatory cells and tumor mutational status.

PMID: 29526824 [PubMed - as supplied by publisher]

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