Increased PD-1 Level in Severe Cervical Injury Is Associated With the Rare Programmed Cell Death 1 (PDCD1) rs36084323 A Allele in a Dominant Model
| Autor: | Christina Alves Peixoto, Norma Lucena-Silva, Eduardo Antônio Donadi, Fabiana Oliveira dos Santos Gomes, Fernanda Silva Medeiros, Thailany Thays Gomes, Maria Carolina Valença Rygaard, Stefan Welkovic, Matheus Costa e Silva, Larissa Albuquerque Paiva, Maria Luiza Bezerra Menezes, Neila Caroline Henrique da Silva, Mauro César da Silva |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Microbiology (medical) HPV Immunology Population Programmed Cell Death 1 Receptor Apoptosis Cervical intraepithelial neoplasia Microbiology polymorphism Lesion 03 medical and health sciences 0302 clinical medicine Cellular and Infection Microbiology Genotype PD-1 medicine cancer Humans Allele CIN education Alleles Original Research Cervical cancer education.field_of_study business.industry Papillomavirus Infections Wild type HPV infection medicine.disease Uterine Cervical Dysplasia QR1-502 030104 developmental biology Infectious Diseases inflammation 030220 oncology & carcinogenesis Female medicine.symptom business |
| Zdroj: | Frontiers in Cellular and Infection Microbiology Frontiers in Cellular and Infection Microbiology, Vol 11 (2021) |
| ISSN: | 2235-2988 |
| Popis: | The high-risk oncogenic human papillomavirus (HPV) has developed mechanisms for evasion of the immune system, favoring the persistence of the infection. The chronic inflammation further contributes to the progression of tissue injury to cervical cancer. The programmed cell death protein (PD-1) after contacting with its ligands (PD-L1 and PD-L2) exerts an inhibitory effect on the cellular immune response, maintaining the balance between activation, tolerance, and immune cell-dependent lesion. We evaluated 295 patients exhibiting or not HPV infection, stratified according to the location (injured and adjacent non-injured areas) and severity of the lesion (benign, pre-malignant lesions). Additionally, we investigated the role of the promoter region PDCD1 -606G>A polymorphism (rs36084323) on the studied variables. PD-1 and PDCD1 expression were evaluated by immunohistochemistry and qPCR, respectively, and the PDCD1 polymorphism was evaluated by nucleotide sequencing. Irrespective of the severity of the lesion, PD-1 levels were increased compared to adjacent uninjured areas. Additionally, in cervical intraepithelial neoplasia (CIN) I, the presence of HPV was associated with increased (P = 0.0649), whereas in CIN III was associated with decreased (P = 0.0148) PD-1 levels, compared to the uninjured area in absence of HPV infection. The PDCD1 -606A allele was rare in our population (8.7%) and was not associated with the risk for development of HPV infection, cytological and histological features, and aneuploidy. In contrast, irrespective of the severity of the lesion, patients exhibiting the mutant PDCD1 -606A allele at single or double doses exhibited increased protein and gene expression when compared to the PDCD1 -606GG wild type genotype. Besides, the presence of HPV was associated with the decrease in PDCD1 expression and PD-1 levels in carriers of the -606 A allele presenting severe lesions, suggesting that other mediators induced during the HPV infection progression may play an additional role. This study showed that increased PD-1 levels are influenced by the -606G>A nucleotide variation, particularly in low-grade lesions, in which the A allele favors increased PDCD1 expression, contributing to HPV immune system evasion, and in the high-grade lesion, by decreasing tissue PD-1 levels. |
| Databáze: | OpenAIRE |
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