A Comprehensive Expression Analysis of Cancer Testis Antigens in Head and Neck Squamous Cell Carcinoma Revels MAGEA3/6 as a Marker for Recurrence.

Fernando Tadeu Zamunér,Carlos Roberto Dos Santos,Bruno Takao Real Karia,Cleyton Zanardo De Oliveira,André Lopes Carvalho,André Luiz Vettore

doi:10.1158/1535-7163.mct-14-0796

Abstract

Despite significant advances in the treatment of head and neck squamous cell carcinoma (HNSCC), the survival rate has not changed in the last decades. Therefore, the development of novel therapeutic strategies is pursued. Cancer-testis antigens (CTA) are strong immunogenic proteins with a tumor-restricted expression pattern, and are considered ideal targets for tumor-specific immunotherapeutic approaches. In this study, using an in silico approach, we selected, among 139 previously described CTA, candidates to be evaluated in 89 HNSCC and 20 normal mucosa samples. SPANX-CD (71.9%), MAGEB2 (44.9%), MAGEA1 (44.9%), MAGEB6 (32.6%), and CXORF48 (27.0%) were found frequently expressed in HNSCC, and over 85% of the tumors expressed at least one of these five CTAs. The mRNA positivity of CXORF48, MAGEB6, and CRISP2 presented significant associations with recognized clinical features for poor outcome. Furthermore, MAGEA3/6 positivity was associated with significantly better disease-free survival (DFS, P = 0.014), and the expression of this antigen was shown to be an independent prognostic factor for tumor recurrence. In conclusion, one of five selected CTAs is expressed in at least 85% of the HNSCCs, suggesting a possible usage as target for immunotherapeutic approaches, and the mRNA-positivity for MAGEA3/6 is shown to be an independent marker for DFS.

Highlights

Head and neck squamous cell carcinoma (HNSCC) affects 600,000 new patients worldwide each year [1]
Diagnosis and management of patients with HNSCC have improved through combined efforts in surgery, radiotherapy, and chemotherapy, but long-term survival rate is still around 50% [29]
Novel forms of treatment are urgently needed, and immunotherapy represents an approach that has yet to be fully explored in HNSCC

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) affects 600,000 new patients worldwide each year [1]. Despite significant advances in therapy, the survival rate for these patients has not improved markedly over the past 30 years [2]. Late diagnosis and frequent locoregional recurrences are the most frequent causes of treatment failure. The development of new therapeutic approaches and their integration into current forms of treatment, which include surgery, radiotherapy, and chemotherapy, are pursued to improve this prognosis. The recent discovery of tumor antigens has opened new doors for specific tumor-targeted treatments using passive or active immunotherapeutic strategies.

Methods

Results

Conclusion