Immune-Related Gene Expression Profiling After PD-1 Blockade in Non–Small Cell Lung Carcinoma, Head and Neck Squamous Cell Carcinoma, and Melanoma
Top Cited Papers
- 1 July 2017
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 77 (13), 3540-3550
- https://doi.org/10.1158/0008-5472.can-16-3556
Abstract
Antibody targeting of the immune checkpoint receptor PD1 produces therapeutic activity in a variety of solid tumors, but most patients exhibit partial or complete resistance to treatment for reasons that are unclear. In this study, we evaluated tumor specimens from 65 patients with melanoma, lung nonsquamous, squamous cell lung or head and neck cancers who were treated with the approved PD1-targeting antibodies pembrolizumab or nivolumab. Tumor RNA before anti-PD1 therapy was analyzed on the nCounter system using the PanCancer 730-Immune Panel, and we identified 23 immune-related genes or signatures linked to response and progression-free survival (PFS). In addition, we evaluated intra- and interbiopsy variability of PD1, PD-L1, CD8A, and CD4 mRNAs and their relationship with tumor-infiltrating lymphocytes (TIL) and PD-L1 IHC expression. Among the biomarkers examined, PD1 gene expression along with 12 signatures tracking CD8 and CD4 T-cell activation, natural killer cells, and IFN activation associated significantly with nonprogressive disease and PFS. These associations were independent of sample timing, drug used, or cancer type. TIL correlated moderately (∼0.50) with PD1 and CD8A mRNA levels and weakly (∼0.35) with CD4 and PD-L1. IHC expression of PD-L1 correlated strongly with PD-L1 (0.90), moderately with CD4 and CD8A, and weakly with PD1. Reproducibility of gene expression in intra- and interbiopsy specimens was very high (total SD Cancer Res; 77(13); 3540–50. ©2017 AACR.Keywords
Other Versions
This publication has 48 references indexed in Scilit:
- Signatures of mutational processes in human cancerNature, 2013
- Tumor Immunotherapy Directed at PD-1The New England Journal of Medicine, 2012
- Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in CancerThe New England Journal of Medicine, 2012
- The blockade of immune checkpoints in cancer immunotherapyNature Reviews Cancer, 2012
- Molecular Insights on the Peripheral and Intratumoral Effects of Systemic High-Dose rIL-2 (Aldesleukin) Administration for the Treatment of Metastatic MelanomaClinical Cancer Research, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- MapSplice: Accurate mapping of RNA-seq reads for splice junction discoveryNucleic Acids Research, 2010
- Biological Processes Associated with Breast Cancer Clinical Outcome Depend on the Molecular SubtypesClinical Cancer Research, 2008
- Type, Density, and Location of Immune Cells Within Human Colorectal Tumors Predict Clinical OutcomeScience, 2006
- HER2 Testing by Local, Central, and Reference Laboratories in Specimens From the North Central Cancer Treatment Group N9831 Intergroup Adjuvant TrialJournal of Clinical Oncology, 2006