Understanding HLA-G driven journey from HPV infection to cancer cervix: Adding missing pieces to the jigsaw puzzle. (November 2020)

• Record Type: Journal Article
• Authors: Aggarwal, Ritu; Sharma, Madhulika; Mangat, Navdeep; Suri, Vanita; Bhatia, Tanvi; Kumar, Prashant; Minz, Ranjana
• Is Part Of: Journal of reproductive immunology. Volume 142(2020)
• Publication Date: 2020-11
• Subjects: Soluble HLA-G -- Membrane-bound HLA-G -- Cervical carcinoma -- Human papillomavirus -- Western blot -- ELISA; Reproduction -- Immunological aspects -- Periodicals; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Reproduction -- Periodicals; Reproduction -- Immunologie -- Périodiques; Immunologie -- Périodiques; Immunology; Reproduction -- Immunological aspects; Periodicals; Electronic journals; Electronic journals; 615.766
• DOI: 10.1016/j.jri.2020.103205
• Languages: English
• ISSNs: 0165-0378

Abstract

Highlights: Fresh tissue samples from normal cervix, HPV infected cervix and cervical carcinoma were utilized. Significant variation of HLA-G expression was observed in the tissue samples among the 3 groups. The soluble HLA-G in plasma samples was significantly elevated in women with cancer cervix. Increased expression of HLA-G in HPV infected cervix (pairwise comparison). Our observations merit exploring the therapeutic role of HLA-G antibodies for cervical cancer. 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 (P < 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 (P < 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.