The Immune Microenvironment, Genome-wide Copy Number Aberrations, and Survival in Mesothelioma Bibhusal Thapa, FCPS, Adriana Salcedo, MSc, Xihui Lin,

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The Immune Microenvironment, Genome-wide Copy Number Aberrations, and Survival in Mesothelioma Bibhusal Thapa, FCPS, Adriana Salcedo, MSc, Xihui Lin, BSc, Marzena Walkiewicz, MSc, Carmel Murone, PhD, Malaka Ameratunga, M.B.B.S., Khashyar Asadi, FRACPA, Siddhartha Deb, M.B.B.S., Stephen Arthur Barnett, FRACS, Simon Knight, FRACS, Paul Mitchell, FRACP, D. Neil Watkins, PhD, Paul C. Boutros, PhD, Thomas John, PhD Journal of Thoracic Oncology Volume 12, Issue 5, Pages 850-859 (May 2017) DOI: 10.1016/j.jtho.2017.02.013 Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Representative images of the immunohistochemistry for programmed death ligand 1 (PD-L1), cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), and forkhead box P3 (FOXP3). (A) PD-L1–negative. (B) Weakly PD-L1–positive. (C) Highly PD-L1–positive. (D) High infiltration with CD4-positive cells. (E) High infiltration with CD8-positive cells. (F) High infiltration with FOXP3-positive cells. (G) Low infiltration with CD4-positive cells. (H) Low infiltration with CD8-positive cells. (I) Low infiltration with FOXP3-positive cells. Journal of Thoracic Oncology 2017 12, 850-859DOI: (10.1016/j.jtho.2017.02.013) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Overall survival and correlation with histological subtype and programmed death ligand 1 (PD-L1) status. (A) Kaplan-Meier (KM) curve based on the whole cohort. (B) KM curve by histological subtype. (C) KM curve by PD-L1 in the whole cohort. (D) KM curve by PD-L1 in epithelioid tumors. (E) KM by PD-L1 in nonepithelioid tumors. Journal of Thoracic Oncology 2017 12, 850-859DOI: (10.1016/j.jtho.2017.02.013) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Consensus clustering based on copy number profile. Each row represents a tumor sample, and genomic regions are represented in columns. The bar graph displays the percent genome aberration (PGA) in individual tumor samples. C1, cluster 1; C2, cluster 2; CNA, copy number aberration; PD-L1, programmed death ligand 1; CDK6, cyclin-dependent kinase 6 gene; MET, MNNG HOS Transforming gene; CDKN2A, cyclin-dependent kinase inhibitor 2A gene; HOXB2, homeobox B2 gene; TIMP2, metallopeptidase inhibitor 2 gene; PGA, per cent genome aberration. Journal of Thoracic Oncology 2017 12, 850-859DOI: (10.1016/j.jtho.2017.02.013) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 4 Percent genome aberration (PGA) and its relationship with programmed death ligand 1 (PD-L1) status and overall survival. (A) Boxplots comparing PGA among groups with differing PD-L1 expression. p Value from Mann-Whitney U test. (B) Kaplan-Meier curves comparing survival in PGA groups in the whole cohort and the Cox proportional hazard p value controlling for age and stratified by histological subtype. PGA is divided between the lower and two upper tertiles. (C) Kaplan-Meier curves comparing survival in PGA groups in epithelioid malignant pleural mesothelioma. Abbreviation: HR, hazard ratio. Journal of Thoracic Oncology 2017 12, 850-859DOI: (10.1016/j.jtho.2017.02.013) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions