Multiparametric profiling of non–small-cell lung cancers reveals distinct immunophenotypes

作者：Patrick Hall Lizotte, Elena V. Ivanova, Mark Magdi Awad, Robert Emmet Jones, Lauren Keogh, Hongye Liu, Ruben Dries, Christina G. Almonte, Grit Sophie Herter-Sprie, Abigail A. Santos, Nora B. Feeney, Cloud Peter Paweletz, Meghana M. Kulkarni, Adam Joel Bass, Anil K. Rustgi, Guo‐Cheng Yuan, Donald W. Kufe, Pasi Antero Janne, Peter S. Hammerman, Lynette Marie Sholl, Frank Stephen Hodi, William G. Richards, Raphael Bueno, Jessie M. English, Mark A. Bittinger, Kwok‐Kin Wong · 发表于：JCI Insight · 年份：2016 · DOI：10.1172/jci.insight.89014 · 被引用次数：128 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Immunotherapy and Biomarkers、Cancer Genomics and Diagnostics

BACKGROUND. Immune checkpoint blockade improves survival in a subset of patients with non–small-cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. METHODS. We performed comprehensive flow cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next-generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC). RESULTS. Cytometric profiling identified an immunologically “hot” cluster with abundant CD8 + T cells expressing high levels of PD-1 and TIM-3 and an immunologically “cold” cluster with lower relative abundance of CD8 + T cells and expression of inhibitory markers. The “hot” cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function and high PD-L1 expression by IHC. There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the “hot” cluster. Additionally, approximately 20% of cases had high B cell infiltrates with a subset producing IL-10. CONCLUSIONS. Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer. FUNDING. The Robert A. and Renée E. Belf...