Differential expression and significance of PD-L1, IDO-1, and B7-H4 in human lung cancer

Kurt A. Schalper, Daniel Carvajal-Hausdorf, Joseph McLaughlin, Mehmet Altan, Vamsidhar Velcheti, Patricia Gaule, Miguel F. Sanmamed, Lieping Chen, Roy S. Herbst, David L. Rimm

Research output: Contribution to journalArticle

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 coexpression. 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.

Original languageEnglish (US)
Pages (from-to)370-378
Number of pages9
JournalClinical Cancer Research
Volume23
Issue number2
DOIs
StatePublished - Jan 15 2017
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Schalper, K. A., Carvajal-Hausdorf, D., McLaughlin, J., Altan, M., Velcheti, V., Gaule, P., Sanmamed, M. F., Chen, L., Herbst, R. S., & Rimm, D. L. (2017). Differential expression and significance of PD-L1, IDO-1, and B7-H4 in human lung cancer. Clinical Cancer Research, 23(2), 370-378. https://doi.org/10.1158/1078-0432.CCR-16-0150