Local immunosuppression induced by high viral load of human papillomavirus: characterization of cellular phenotypes producing interleukin‐10 in cervical neoplastic lesions

Summary A specific immune response to human papillomavirus (HPV) in the cervical microenvironment plays a key role in eradicating infection and eliminating mutated cells. However, high‐risk HPVs modulate immune cells to create an immunosuppressive microenvironment, and induce these immune cells to p...

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Bibliographic Details
Published in:Immunology 2015-09, Vol.146 (1), p.113-121
Main Authors: Prata, Thiago Theodoro Martins, Bonin, Camila Mareti, Ferreira, Alda Maria Teixeira, Padovani, Cacilda Tezelli Junqueira, Fernandes, Carlos Eurico dos Santos, Machado, Ana Paula, Tozetti, Inês Aparecida
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aging
Cervical Intraepithelial Neoplasia - immunology
Cervical Intraepithelial Neoplasia - virology
Female
human papillomavirus
Human papillomavirus 16 - immunology
Human papillomavirus 18 - immunology
Humans
Immune Tolerance - immunology
immunosuppression
Interleukin-10 - biosynthesis
Interleukin-10 - immunology
interleukin‐10
Keratinocytes - metabolism
Langerhans Cells - metabolism
Macrophages - metabolism
Middle Aged
Original
Papillomavirus Infections - immunology
Papillomavirus Infections - virology
Tumor Microenvironment - immunology
Uterine Cervical Neoplasms - immunology
Uterine Cervical Neoplasms - virology
Viral Load
Young Adult
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Summary:Summary A specific immune response to human papillomavirus (HPV) in the cervical microenvironment plays a key role in eradicating infection and eliminating mutated cells. However, high‐risk HPVs modulate immune cells to create an immunosuppressive microenvironment, and induce these immune cells to produce interleukin 10 (IL‐10). This production of IL‐10, in conjunction with HPV infection, contributes to the appearance of cervical neoplastic lesions. We sought to characterize the IL‐10‐producing cellular phenotype, and investigate the influence of host and HPV factors upon the induction of an immunosuppressive microenvironment. Immunohistochemical analysis demonstrated an increase in IL‐10 production by keratinocytes, macrophages and Langerhans cells in high‐grade cervical lesions and cervical cancer. This increase was more pronounced in patients older than 30 years, and was also correlated with high viral load, and infection with a single HPV type, particularly high‐risk HPVs. Our results indicate the existence of a highly immunosuppressive microenvironment composed of different IL‐10‐producing cellular phenotypes in cervical cancer samples, and samples classified as high‐grade cervical lesions (cervical intraepithelial neoplasia stages II and III). The immunosuppressive microenvironment that developed for these different cellular phenotypes favours viral persistence and neoplastic progression.
ISSN:0019-2805
1365-2567
DOI:10.1111/imm.12487