TY - JOUR
T1 - Characterization of the T-cell receptor repertoire and immune microenvironment in patients with locoregionally advanced squamous cell carcinoma of the head and neck
AU - Saloura, Vassiliki
AU - Fatima, Aiman
AU - Zewde, Makda
AU - Kiyotani, Kazuma
AU - Brisson, Ryan
AU - Park, Jae Hyun
AU - Ikeda, Yuji
AU - Vougiouklakis, Theodore
AU - Bao, Riyue
AU - Khattri, Arun
AU - Seiwert, Tanguy
AU - Cipriani, Nicole
AU - Lingen, Mark
AU - Vokes, Everett
AU - Nakamura, Yusuke
N1 - Publisher Copyright:
©2017 AACR.
PY - 2017/8/15
Y1 - 2017/8/15
N2 - 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 ¼ 0.049). Higher GRZB levels correlated significantly with longer recurrence-free survival (log-rank, P ¼ 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.
AB - 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 ¼ 0.049). Higher GRZB levels correlated significantly with longer recurrence-free survival (log-rank, P ¼ 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.
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U2 - 10.1158/1078-0432.CCR-17-0103
DO - 10.1158/1078-0432.CCR-17-0103
M3 - Article
C2 - 28442504
AN - SCOPUS:85028081008
SN - 1078-0432
VL - 23
SP - 4897
EP - 4907
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 16
ER -