Format

Send to

Choose Destination
Clin Cancer Res. 2017 Jan 15;23(2):370-378. doi: 10.1158/1078-0432.CCR-16-0150. Epub 2016 Jul 20.

Differential Expression and Significance of PD-L1, IDO-1, and B7-H4 in Human Lung Cancer.

Author information

1
Department of Pathology, Yale School of Medicine, New Haven, Connecticut. kurt.schalper@yale.edu.
2
Medical Oncology Section, Yale School of Medicine, New Haven, Connecticut.
3
Translational Immuno-oncology Laboratory, Yale Cancer Center, New Haven, Connecticut.
4
Department of Pathology, Yale School of Medicine, New Haven, Connecticut.
5
Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio.
6
Immunobiology, Yale School of Medicine, New Haven, Connecticut.

Abstract

PURPOSE:

To determine the expression level, associations, and biological role of PD-L1, IDO-1, and B7-H4 in non-small cell lung cancer (NSCLC).

EXPERIMENTAL DESIGN:

Using multiplexed quantitative immunofluorescence (QIF), we measured the levels of PD-L1, IDO-1, B7-H4, and different tumor-infiltrating lymphoycte (TIL) subsets in 552 stages I-IV lung carcinomas from two independent populations. Associations between the marker levels, TILs, and major clinicopathologic variables were determined. Validation of findings was performed using mRNA expression data from The Cancer Genome Atlas (TCGA) and in vitro stimulation of lung adenocarcinoma A549 cells with IFNγ and IL10.

RESULTS:

PD-L1 was detected in 16.9% and 21.8% of cases in each population. IDO-1 was expressed in 42.6% and 49.8%; and B7-H4 in 12.8% and 22.6% of cases, respectively. Elevated PD-L1 and IDO-1 were consistently associated with prominent B- and T-cell infiltrates, but B7-H4 was not. Coexpression of the three protein markers was infrequent, and comparable results were seen in the lung cancer TCGA dataset. Levels of PD-L1 and IDO-1 (but not B7-H4) were increased by IFNγ stimulation in A549 cells. Treatment with IL10 upregulated B7-H4 but did not affect PD-L1 and IDO-1 levels.

CONCLUSIONS:

PD-L1, IDO-1, and B7-H4 are differentially expressed in human lung carcinomas and show limited co-expression. While PD-L1 and IDO-1 are associated with increased TILs and IFNγ stimulation, B7-H4 is not. The preferential expression of discrete immune evasion pathways in lung cancer could participate in therapeutic resistance and support design of optimal clinical trials. Clin Cancer Res; 23(2); 370-8. ©2016 AACR.

PMID:
27440266
PMCID:
PMC6350535
DOI:
10.1158/1078-0432.CCR-16-0150
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center