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Lung Adenocarcinoma and Squamous Cell Carcinoma Gene Expression Subtypes Demonstrate Significant Differences in Tumor Immune Landscape  Hawazin Faruki,

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Presentation on theme: "Lung Adenocarcinoma and Squamous Cell Carcinoma Gene Expression Subtypes Demonstrate Significant Differences in Tumor Immune Landscape  Hawazin Faruki,"— Presentation transcript:

1 Lung Adenocarcinoma and Squamous Cell Carcinoma Gene Expression Subtypes Demonstrate Significant Differences in Tumor Immune Landscape  Hawazin Faruki, DrPH, Gregory M. Mayhew, DrPH, Jonathan S. Serody, MD, D. Neil Hayes, MD, Charles M. Perou, PhD, Myla Lai- Goldman, MD  Journal of Thoracic Oncology  Volume 12, Issue 6, Pages (June 2017) DOI: /j.jtho Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

2 Figure 1 Heatmaps of Bindea et al.6 showing immune cell signature expression, other immune signatures, and individual immune markers in lung adenocarcinoma and squamous cell carcinoma gene expression data sets.1,2 TRU, terminal respiratory unit; PP, proximal proliferative; PI, proximal inflammatory; Tcm, central memory T cell; Tem, effector memory T cell; Th1, type 1 T helper cell; Th2, type 2 T helper cell; TFH, T follicular helper cell; Th17, T-helper 17 cell; Treg, regulatory T cell; Tγδ, γδ T cell; NK, natural killer; DC, dendritic cell; iDC, immature dendritic cell; aDC, activated dendritic cell; pDC, plasmacytoid dendritic cell; IFN, interferon; PD-L1, programmed death ligand 1; PD-L2, programmed death ligand 2; PDCD1, programmed cell death 1; CTLA4, cytotoxic T-lymphocyte associated protein 4; MHC II, major histocompatibility complex class II. Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

3 Figure 2 Association strength (adjusted r2) between CD274 molecule gene (CD274) (programmed death ligand 1 [PD-L1]) expression and immune signature versus strength between subtype and immune signature for 13 adaptive immune cell (AIC) expression signatures in adenocarcinoma (AD) and squamous cell carcinoma (SCC) data sets. Association between subtype and AIC was greater for some AICs in AD and for all AICs tested in SCC. Tcm, central memory T cell; Tem, effector memory T cell; Th1, type 1 T helper cell; Th2, type 2 T helper cell; TFH, T follicular helper cell; Th17, T helper 17 cell; Treg, regulatory T cell; Tγδ, γδ T cell. Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

4 Figure 3 Reproducibility of T-cell signature gene expression subtype patterns across multiple adenocarcinoma data sets2,4,17,18 and squamous cell carcinoma data sets.1,3,16,20 RNA sequencing (RNA-Seq Kit [Illumina, San Diego, CA]) and microarrays from both Affymetrix (Santa Clara, CA) and Agilent (Santa Clara, CA). TCGA, The Cancer Genome Atlas; TRU, terminal respiratory unit; PP, proximal proliferative; PI, proximal inflammatory. Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

5 Figure 4 Adenocarcinoma (AD) and squamous cell carcinoma (SCC) subtype nonsilent mutation burden (A and B), serine/threonine kinase 11 gene (STK11) inactivation (mutation and/or deletion) in AD (C), nuclear factor erythroid 2, like 2 gene (NFE2L2) expression in SCC (D), and major histocompatibility complex class II (MHC II) signature (E and F) with association test p values. Mb, megabase; TRU, terminal respiratory unit; PP, proximal proliferative; PI, proximal inflammatory. Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

6 Figure 5 Subtype-specific immune marker hazard ratios and 95% confidence intervals (CIs) for 5-year overall survival in stage I to III adenocarcinoma (A) and stage I to III squamous cell carcinoma (B). Hazard ratios (HRs) correspond to a unit increase in the normalized immune marker and were adjusted for pathological stage using Cox models. Only markers that were significant (nominal p value <0.05) for at least one subtype are shown. Th1, type 1 T helper cells; Th2, type 2 T helper cells; TFH, T follicular helper cell; Th17, T helper 17 cell; Treg, regulatory T cell; DC, dendritic cell; iDC, immature dendritic cell; PD-L1, programmed death ligand 1; CTLA4, cytotoxic T-lymphocyte associated protein 4; MHC II, major histocompatibility complex class II; TRU, terminal respiratory unit; PP, proximal proliferative; PI, proximal inflammatory. Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

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