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Supplementary Figure S1 from CD44+ Cells in Head and Neck Squamous Cell Carcinoma Suppress T-Cell–Mediated Immunity by Selective Constitutive and Inducible Expression of PD-L1

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posted on 2023-03-31, 18:11 authored by Yunqin Lee, June Ho Shin, Michelle Longmire, Hua Wang, Holbrook E. Kohrt, Howard Y. Chang, John B. Sunwoo

Supplementary Figure S1. Gating strategy for isolating tumor cells from primary SCCHN tumors and xenografts.

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ARTICLE ABSTRACT

Purpose: Human tumors consist of heterogeneous populations of cells with distinct marker expression and functional properties. In squamous cell carcinoma of the head and neck (SCCHN), CD44 is a well-characterized marker of a resilient subpopulation of cells associated with increased tumorigenesis, radioresistance, and chemoresistance. Evidence indicates that these cells have an immunosuppressive phenotype; however, mechanisms have been elusive.Experimental Design: Using primary human SCCHN tumor samples and patient-derived xenografts, we examined the phenotypes of subsets of tumor cells and investigated mechanisms regulating their immunogenicity.Results: CD44+ cells in primary human SCCHN were found to have an epithelial-to-mesenchymal (EMT) phenotype and were less immunogenic than CD44− cells when cultured with autologous CD8+ tumor-infiltrating T cells. Selective expression of the programmed death-ligand 1 (PD-L1) was observed on CD44+ cells compared with CD44− cells and was associated with constitutive phosphorylation of STAT3 on CD44+ cells. Importantly, inhibition of STAT3 decreased expression of PD-L1 on CD44+ cells. IFNγ treatment preferentially induced even further PD-L1 expression on CD44+ cells and was associated with enhanced IFNγ receptor expression and phosphorylation of STAT1. Finally, the decreased immunogenicity of CD44+ cells was partially reversed by antibody blockade of the programmed death 1 (PD-1) receptor, indicating that the differences in PD-L1 expression between CD44+ and CD44− cells are biologically and clinically relevant.Conclusions: Our findings provide a mechanism by which long-lived CD44+ tumor-initiating cells can selectively evade host immune responses and provide rationale for targeting the PD-1 pathway in the adjuvant therapy setting of SCCHN. Clin Cancer Res; 22(14); 3571–81. ©2016 AACR.

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