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. To develop a more comprehensive knowledge of the NSCLC tumor immune landscape, 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). Cytometric profiling identified two main tumor immunophenotypes: an immunologically “hot” cluster with high abundance of CD8+ T cells expressing high levels of the inhibitory receptors 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 by mRNA analysis, and high PD-L1 expression by IHC. Within the “hot” cluster there was a small subgroup with high granulocytic infiltrates and lower relative T cell abundance, but with high expression of inhibitory receptors by T cells. There was no correlation between immunophenotype and KRAS or EGFR mutation status, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the “hot” cluster. Additionally, ∼20% of cases had high B cell infiltrates and we demonstrate that a subset of these cells display characteristics of immunosuppressive IL-10-producing cells. Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer.
Citation Format: Patrick Lizotte, Elena Ivanova, Mark Bittinger, Kwok-Kin Wong. Multi-parametric profiling of non-small cell lung cancers reveals distinct immunophenotypes [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A132.
- ©2016 American Association for Cancer Research.