Abstract
Introduction: Human papillomavirus (HPV) persistent infection is the leading cause of cervical cancer and its precursor lesions, and the inappropriate immune response is among the factors that contribute to viral persistence. This may be influenced by regulatory T (Treg) cells and the production of immunosuppressive cytokines, such as transforming growth factor beta (TGF-β) and interleukin-10 (IL-10). Objective: We established the profile of the predominant response, Th1 or immunosuppressive response, in the tissue microenvironment, by detecting interferon-gamma (IFN-γ), TGF-β, and IL-10, as well as the co-expression of IL-2 receptor alpha (CD25) and forkhead box P3 (FOXP3). Methods: Seventy-four samples from uterine cervix biopsies that underwent HPV deoxyribonucleic acid (DNA) detection and histopathology analysis were immunostained to detect CD25/FOXP3, IFN-γ and suppressive cytokines in lymphocytes. Results: The microenvironment of high-grade squamous intraepithelial lesion (HSIL) samples with high numbers of viral particles (≥ 10,000 copies/ml) contained high numbers of CD25/FOXP3+, TGF-β+, IL-10+, and IFN-γ+ cells. Conclusion: The co-expression of CD25/FOXP3 and the expression of TGF-β, and IL-10 in HSIL samples suggest the existence of Treg cells in these locations, although IFN-γ expression was observed in several cells in these samples. Our data suggest that this cytokine could be related to immunosuppressed microenvironment maintenance, favoring the persistent HPV infection and the progression to carcinoma.
Highlights
Human papillomavirus (HPV) persistent infection is the leading cause of cervical cancer and its precursor lesions, and the inappropriate immune response is among the factors that contribute to viral persistence
In the present study, we aimed to detect the co-expression of the markers CD25/forkhead box P3 (FOXP3) and the expression of IFN-γ, IL-10, and TGF-β in lymphocytes, by performing immunohistochemistry, to help elucidate the prevailing T helper response profile (Th1 or immunosuppressive response) in the HPVinfected microenvironment, and to provide a better understanding of the pathological processes associated with persistence or regression of the infection, or progression to the malignant form
HPV16 was present in 44.7% (21/47) of the high-grade squamous intraepithelial lesion (HSIL) samples and 50% (6/12) of carcinoma samples, while HPV 18 was found in 48.6% (22/47) of the HSIL samples and 50% of the carcinoma samples too (Table 2)
Summary
Human papillomavirus (HPV) persistent infection is the leading cause of cervical cancer and its precursor lesions, and the inappropriate immune response is among the factors that contribute to viral persistence. This may be influenced by regulatory T (Treg) cells and the production of immunosuppressive cytokines, such as transforming growth factor beta (TGF-β) and interleukin-10 (IL-10). IFN-γ is a dominant cytokine that polarizes Th cells for the Th1 phenotype and inhibits the development of Th2 cells[4] This polarization plays a crucial role in the host defense against viral infection and tumor development[9]
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