Understanding HLA-G driven journey from HPV infection to cancer cervix: Adding missing pieces to the jigsaw puzzle.
J Reprod Immunol
; 142: 103205, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-33099242
ABSTRACT
Human Papillomavirus (HPV) is a vital risk-factor for cancer cervix. However, persistent HPV infection results in cervical cancer in only a minority. Probably, HPV subdues the host immune response for persistence, which includes augmentation of HLA-G and plausibly aids in progression to cervical cancer. HLA-G, which comprises of membrane and soluble form, downregulates the host's immune response and generate tolerance. The current study aimed to analyze both forms of HLA-G in fresh tissue and plasma of women with HPV-infected and uninfected cervix and cancer cervix using Western blot and ELISA. The study cohort included 30 women with cervical carcinoma and equal number with normal cervix and 6 with HPV infected cervix. We observed a significant upregulation of membranous HLA-G expression in HPV infected cervix and cervical carcinoma (Pâ¯<â¯0.001). Interestingly, the pairwise comparison of HLA-G tissue protein expression of the normal cervix and cervical carcinoma, as well as the normal cervix with HPV infected cervix, was significant (Pâ¯<â¯0.001). Levels of soluble HLA-G were significantly raised in carcinoma cervix. We observed a progressive increase in HLA-G protein expression in HPV infected cervix and cervical carcinoma. These findings compel us to hypothesize that the upregulation of HLA-G expression favors the persistence of HPV in a microenvironment of a submissive host response. This progressive upregulation further leads to cervical cancer. Thus elimination of HPV infection seems to be a desirable proposition to prevent cervical cancer. In the absence of antiviral therapy for HPV, exploration of HLA-G antibody-based therapeutic strategies appear promising.
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MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
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Displasia do Colo do Útero
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Neoplasias do Colo do Útero
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Infecções por Papillomavirus
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Antígenos HLA-G
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article