No abstract

No 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 HPVpositive 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.

No abstract

3080 Background: Immunotherapy with checkpoint blockade was recently approved for patients with recurrent/metastatic SCCHN, however it has not been investigated in the curative-intent setting yet. In this study, we investigated the T-cell receptor repertoire and the immune microenvironment in tumor tissues of SCCHN patients with locoregionally advanced disease. Methods: T-cell receptor sequencing and polymerase chain reaction for immune-related genes of tumor tissues from 44 patients with locoregionally advanced SCCHN prior to treatment with definitive chemoradiotherapy were conducted. T-cell receptor clonality and the mRNA expression levels of immune-related genes were correlated with various clinicopathological parameters. Results: In patients with locoregionally advanced SCCHN, tumor infiltrating T-cells clonally expand and GRZB mRNA levels were associated significantly with longer progression-free survival (PFS) (p = 0.003) independent of HPV status, tumor and nodal stage. The TCR-β DI was significantly lower in HPV-negative compared to HPV-positive tumors (p = 0.002), signifying more clonal T-cell expansion in HPV-negative tumors. A higher percentage of HPV-negative tumors expressed HLA-A protein compared to HPV-positive tumors (p = 0.049), suggesting that the greater T-cell clonal expansion might be due to more robust antigen presentation by HPV-negative tumors. Conclusions: This study suggests the pre-existence of clonally expanded T-cells in patients with locoregionally advanced SCCHN prior to treatment, and provides rationale to introduce immunotherapy in the curative-intent setting. The association of high GRZB mRNA levels with favorable PFS independent of HPV-status, tumor and nodal stage supports that the pre-existence of an intrinsically inflamed microenvironment enhances chemoradiotherapy effects. Finally, in HPV-positive tumors, the T-cell infiltrate seemed to be more diverse which could be secondary to virally-induced defective expression of HLA class I molecules.