Predictive Value of CD8 Expression and FoxP3 Methylation in Nasopharyngeal Carcinoma Patients Treated with Chemoradiotherapy in a Non-endemic Area

Autor: Damiana Antonia Faè, Riccardo Dolcetti, Debora Martorelli, Luigi Barzan, Carlo Gobitti, E. Comaro, F. Navarria, C. Furlan, Giuseppe Fanetti, Sandro Sulfaro, Elena Muraro, Agostino Steffan, Giovanni Franchin, Chiara Pratesi, Stefania Zanussi, Emanuela Vaccher, Valentina Lupato, Jerry Polesel, Michela Cangemi, Vittorio Giacomarra, Vincenzo Canzonieri, C. Scaini, Giuseppe Grando, Elisabetta Fratta
Přispěvatelé: Muraro, E., Vaccher, E., Furlan, C., Fratta, E., Fanetti, G., Fae', D. A., Martorelli, D., Cangemi, M., Polesel, J., Navarria, F., Gobitti, C., Comaro, E., Scaini, C., Pratesi, C., Zanussi, S., Lupato, V., Grando, G., Giacomarra, V., Sulfaro, S., Barzan, L., Dolcetti, R., Steffan, A., Canzonieri, V., Franchin, G.
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Oncology
Epstein-Barr Virus Infections
Cancer Research
medicine.medical_treatment
Radiation Tolerance
0302 clinical medicine
Tumor Microenvironment
CD8
Chemoradiotherapy
EBV-specific immunity
FoxP3
Immunosuppression
Nasopharyngeal carcinoma
ELISPOT
FOXP3
Forkhead Transcription Factors
General Medicine
Middle Aged
medicine.anatomical_structure
030220 oncology & carcinogenesis
Female
Adult
medicine.medical_specialty
Adolescent
CD8 Antigens
T cell
Pathology and Forensic Medicine
Viral Proteins
Young Adult
03 medical and health sciences
Immune system
Predictive Value of Tests
Internal medicine
medicine
Humans
Aged
Retrospective Studies
business.industry
Nasopharyngeal Neoplasms
DNA Methylation
medicine.disease
030104 developmental biology
Drug Resistance
Neoplasm
business
Zdroj: Pathology & Oncology Research. 26:2459-2467
ISSN: 1532-2807
1219-4956
DOI: 10.1007/s12253-020-00859-3
Popis: 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.
Databáze: OpenAIRE
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