American Association for Cancer Research
Browse

Supplementary data from Characterization of the T-Cell Receptor Repertoire and Immune Microenvironment in Patients with Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

Download (13.08 MB)
journal contribution
posted on 2023-03-31, 19:22 authored by Vassiliki Saloura, Aiman Fatima, Makda Zewde, Kazuma Kiyotani, Ryan Brisson, Jae-Hyun Park, Yuji Ikeda, Theodore Vougiouklakis, Riyue Bao, Arun Khattri, Tanguy Seiwert, Nicole Cipriani, Mark Lingen, Everett Vokes, Yusuke Nakamura
<p>Supplementary Figure 1. TCR-β DI in HPV-positive patients (excluding smokers with {greater than or equal to}10packyear history) versus HPV-negative patients (excluding patients with <10pack-year history) (Mann-Whitney U-test, p=0.004). Supplementary Figure 2. Sum of percentages of top 10 CDR3 clonotypes in HPV-positive versus HPV-negative tumors (Mann-Whitney U-test, p=0.01). Supplementary Figure 3. RT-PCR results for CTLA4, PD-1, IDO1, PD-L1, PD-L2, CD206 and FOXP3/CD4 ratio in HPV-positive versus HPV-negative tumors (Mann-Whitney U-test). Supplementary Figure 4. TCR-β DI, recurrence-free survival and overall survival Kaplan-Meier curves. Supplementary Figure 5. TCR-β DI, T-stage, N-stage and tumor localization (Mann-Whitney U- test). Supplementary Figure 6. Significant correlations of GRZB and PRF1 with B7-H3, CD206, FOXP3 and CTLA4 using RT-PCR in tissues from 44 patients with locoregionally advanced SCCHN. Pearson''s correlation co-efficients and p-values are shown for each graph. Supplementary Figure 7. Significant correlations of CD4, CTLA4 and FOXP3 with TCR-β DI using RT-PCR and TCR sequencing in tissues from 43 patients with locoregionally advanced SCCHN. Pearson''s correlation co-efficients and p-values are shown for each graph. Supplementary Figure 8. HLA-A mRNA levels in HPV-positive versus HPV-negative patients (n=44) and association of HLA-A mRNA with TCR-β DI. HLA-A expression (logarithmic scale) was divided by median (T1-T2) and the TCR-β DI (logarithmic scale) was plotted against the HLA-A expression categories. Supplementary Table 1. Univariate and multivariate Cox-regression analysis of overall survival for immune markers and HPV status, tumor and nodal stage.</p>

History

ARTICLE ABSTRACT

Purpose: Squamous cell carcinoma of the head and neck (SCCHN) is a lethal cancer with a suboptimal 5-year overall survival of approximately 50% with surgery and/or definitive chemoradiotherapy. Novel treatments are thus urgently awaited. Immunotherapy with checkpoint blockade has emerged as a promising option for patients with recurrent/metastatic SCCHN; however, it has not been investigated in the curative-intent setting yet. The purpose of this study was to investigate the T-cell receptor repertoire and the tumor microenvironment in tumor tissues of SCCHN patients with locoregionally advanced disease.Experimental Design: We performed T-cell receptor sequencing of tumor tissues from 44 patients with locoregionally advanced SCCHN prior to treatment with definitive chemoradiotherapy and correlated the T-cell clonality and the mRNA expression levels of immune-related genes with clinicopathologic parameters.Results: Clonal expansion of T cells was significantly higher in human papilloma virus (HPV)–negative compared with HPV-positive tumors, signifying more robust antigen presentation in HPV-negative tumors. The latter was supported by the higher percentage of HPV-negative tumors expressing HLA-A protein compared with HPV-positive tumors (P = 0.049). Higher GRZB levels correlated significantly with longer recurrence-free survival (log-rank, P = 0.003) independent of tumor size, nodal stage, and HPV status.Conclusions: Our findings support clonal expansion of T cells in SCCHN patients with locoregionally advanced disease and imply differences in the antigen presentation capacity between HPV-negative and HPV-positive tumors. Elevated GRZB mRNA levels may also serve as a favorable and independent predictor of outcome in SCCHN patients treated with chemoradiotherapy. These data provide rationale for the introduction of immunotherapeutic approaches in the curative-intent setting. Clin Cancer Res; 23(16); 4897–907. ©2017 AACR.

Usage metrics

    Clinical Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC