RESUMEN
The maintenance of homeostasis of the immune system depends on the balance between excitatory and inhibitory signals. Programmed death ligand (PD-L1) is a molecule which downregulates the immune system targeting the programmed death receptor 1 (PD-1). Under physiological conditions, the receptor is constitutively expressed in lymphocytes. The PD-L1 / PD-1 pathway plays a key role in completing the immune response in the right way, preventing excessive stimulation of the cells of the immune system, protecting the organism against autoimmunity. Under pathological conditions PD-L1 expression may take place in tumor cells. Binding of PD-1 to its ligand on tumor cells suppresses T lymphocytes through a negative feedback. This mechanism allows abnormal cells to avoid destruction by the host immune system. The expression of PD-L1 in tumors has been described in many histological types of cancer: melanoma, lung cancer, breast and ovarian, pancreatic and esophagus adenocarcinoma, kidney tumors and bladder cancers as well as in hematopoietic malignancies. Many studies report a significant effect of PD-L1 polymorphisms on clinical parameters of patients. Studies of PD-L1 polymorphisms showed their influence on the stage of cancer, effectiveness of chemotherapy and prognosis after tumor resection. Further analysis of the polymorphisms may result in development of effective therapies that restore anti-tumor immunity. Inhibition of PD-L1 / PD-1 is one of the most promising immunotherapies for various types of cancer. This work was intended to present information about the impact of PD-L1 gene expression and polymorphisms on the clinical parameters of patients with cancer.
Asunto(s)
Antígeno B7-H1/genética , Neoplasias/genética , Polimorfismo Genético , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias/clasificación , Neoplasias/patología , Pronóstico , Receptor de Muerte Celular Programada 1/genéticaRESUMEN
PURPOSE: The current study aimed to examine the association between head and neck squamous cell carcinoma (HNSCC) and infection with different human papillomavirus virus (HPV) subtypes, including analysis of promoter methylation of several genes (APC, CDKN2A, MGMT, CDH1 and TIMP3) and the correlation with their mRNA expression in tumours and surgical margins. METHODOLOGY: In 47 patients with a primary tumour of the oral cavity, HPV detection and identification of 33 subtypes was performed after previous DNA isolation using a GenoFlow HPV Array Test Kit. RESULTS: Fifteen patients (31.92â%) were HPV [+] and the following HPV types were detected: 16 (46.67â%), 18 (6.67â%) and 43/44 (40â%). This study is the first to describe HPV 43/44 subtypes in HNSCC in a Polish population. We noted no clinical significance of HPV [+] HNSCC compared to HPV [-], however, this differed among HPV subtypes. CDKN2A promoter methylation was more frequent in HPV-16/18 patients compared to HPV43/44 patients, but there was no difference in gene expression level between HPV [+] and [-] patients. CONCLUSION: We detected HPV infection in 31.92â% of oral cancer cases. HPV 16, along with HPV 43/44, were the most frequent subtypes. Knowledge of HPV [+] HNSCC biology may be useful in establishing the prognosis and developing novel therapies in future.
Asunto(s)
Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Boca/genética , Neoplasias de la Boca/virología , Infecciones por Papillomavirus/genética , Adulto , Anciano , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , ADN Viral/genética , Femenino , Interacciones Microbiota-Huesped/genética , Humanos , Masculino , Persona de Mediana Edad , Papillomaviridae/clasificación , Regiones Promotoras Genéticas , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Inhibidor Tisular de Metaloproteinasa-3/genéticaRESUMEN
Head and neck squamous cell carcinoma (HNSCC) is one of the leading cancers by incidence worldwide. The risk of these cancers is strictly associated with alkylation factors present in tobacco smoke. The crucial role in preventing DNA alkylation is played by O6-methylguanine-DNA methyltransferase (MGMT). Dysfunction or lack of MGMT is associated with an increased risk of cancer. The aim of the study was to assess the influence of MGMT polymorphisms: rs12917 and rs11016879 on HNSCC risk and course. The study consisted of 69 HNSCC patients and 242 healthy individuals. Case samples were taken from resected tumour tissue. The control group comprised samples of epithelial cells collected from mucous membranes using swabs. DNA samples were genotyped by employing the 5' nuclease assay for allelic discrimination using TaqMan SNP Genotyping Assays. The significance between distributions of genotypes and alleles was tested using Pearson's χ2 test analysis. Our results indicated that the MGMT rs12917 TT genotype increases the risk of HNSCC. The MGMT rs11016879 AG genotype and A allele were associated with increased HNSCC risk. We noted higher risk of nodal metastasis in rs11016879 AA homozygotes. Mechanisms leading to MGMT enzymatic defect are unknown and hence further studies need to be carried out. Our data suggest that the examined polymorphisms may be considered as potential prognostic factors for HNSCC risk and outcome. Further studies are necessary to verify our results.