Predictive Value of CD8 Expression and FoxP3 Methylation in Nasopharyngeal Carcinoma Patients Treated with Chemoradiothe
- PDF / 2,666,860 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 62 Downloads / 194 Views
ORIGINAL ARTICLE
Predictive Value of CD8 Expression and FoxP3 Methylation in Nasopharyngeal Carcinoma Patients Treated with Chemoradiotherapy in a Non-endemic Area E. Muraro 1 & E. Vaccher 2 & C. Furlan 3,4 & E. Fratta 1 & G. Fanetti 4 & D. A. Fae’ 1 & D. Martorelli 1 & M. Cangemi 1 & J. Polesel 5 & F. Navarria 4 & C. Gobitti 4 & E. Comaro 1 & C. Scaini 1 & C. Pratesi 1 & S. Zanussi 1 & V. Lupato 6 & G. Grando 6 & V. Giacomarra 6 & S. Sulfaro 7 & L. Barzan 8 & R. Dolcetti 9 & A. Steffan 1 & V. Canzonieri 10,11 & G. Franchin 4 Received: 1 August 2019 / Accepted: 16 June 2020 # Arányi Lajos Foundation 2020
Abstract Undifferentiated Nasopharyngeal Carcinoma (UNPC) is associated with Epstein-Barr Virus (EBV) and characterized by an abundant immune infiltrate potentially influencing the prognosis. Thus, we retrospectively assessed the significance of immunosuppression in the UNPC microenvironment as prognostic biomarker of treatment failure in a non-endemic area, and monitored the variation of systemic EBV-specific immunity before and after chemoradiotherapy (CRT). DNA and RNA were extracted from diagnostic biopsies obtained by tumor and adjacent mucosa from 63 consecutive EBV+ UNPC patients who underwent radical CRT. Among these patients 11 relapsed within 2 years. The expression of the EBV-derived UNPC-specific BARF1 gene and several immune-related genes was monitored through quantitative RT-PCR and methylation-specific PCR analyses. Peripheral T cell responses against EBV and BARF1 were measured in 14 patients (7 relapses) through IFN-γ ELISPOT assay. We found significantly higher expression levels of BARF1, CD8, IFN-γ, IDO, PD-L1, and PD-1 in UNPC samples compared to healthy tissues. CD8 expression was significantly reduced in both tumor and healthy tissues in UNPC patients who relapsed within two years. We observed a hypomethylated FOXP3 intron 1 exclusively in relapsed UNPC patients. Finally, we noticed a significant decrease in EBV- and BARF1-specific T-cells after CRT only in relapsing patients. Our data suggest that a high level of immunosuppression (low CD8, hypomethylated FoxP3) in UNPC microenvironment may predict treatment failure and may allow an early identification of patients who could benefit from the addition of immune modulating strategies to improve first line CRT. Keywords Nasopharyngeal carcinoma . Immunosuppression . EBV-specific immunity . Chemoradiotherapy . CD8 . FoxP3 Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12253-020-00859-3) contains supplementary material, which is available to authorized users. * E. Muraro [email protected] 1
Immunopathology and Cancer Biomarkers Unit, Department of Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, PN, Italy
2
Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, PN, Italy
3
Department of Radiation Oncology, General Hospital “San Martino”, Belluno, Italy
4
Department of Radiation Oncology, Centro di Riferimento O
Data Loading...
