Modulation of antigen presenting cell functions during chronic HPV infection

Abstract

High-risk human papillomaviruses (HR-HPV) infect basal keratinocytes, where in some individuals they evade host immune responses and persist. Persistent HR-HPV infection of the cervix causes precancerous neoplasia that can eventuate in cervical cancer. Dendritic cells (DCs) are efficient in priming/cross-priming antigen-specific T cells and generating antiviral and antitumor cytotoxic CD8+ T cells. However, HR-HPV have adopted various immunosuppressive strategies, with modulation of DC function crucial to escape from the host adaptive immune response. HPV E6 and E7 oncoproteins alter recruitment and localization of epidermal DCs, while soluble regulatory factors derived from HPV-induced hyperplastic epithelium change DC development and influence initiation of specific cellular immune responses. This review focuses on current evidence for HR-HPV manipulation of antigen presentation in dendritic cells and escape from host immunity.

Indoleamine 2,3‐dioxygenase and tryptophan 2,3‐dioxygenase expression in HPV infection, SILs, and cervical cancer

“…The maintenance of an immunosuppressive microenvironment has an important role in carcinogenesis in general and also in HPV‐associated carcinogenesis . Tumor‐associated macrophages (TAMs), tumor‐infiltrating lymphocytes, and tumor‐associated neutrophils (TANs) are observed in several types of cancers .…”

“…Both granulocytic lineage MDSCs and TANs have gained much more relevance recently and, because of the similarities of their protumoral and phenotypic characteristics, their distinction has not been simple . The transformed epithelium by HPV produces soluble factors and recruits TAMs, tumor‐infiltrating lymphocytes, and MDSCs, which were recently identified in cervical cancer and associated with the expression of tumor granulocyte–colony‐stimulating factor and chemoresistance . In cervical cancer, neutrophils have been considered to have protumoral activity .…”

“…HPV employs multiple strategies for immune evasion, such as low virulence, interference with host cell‐cycle regulators, and inhibition of important components of the innate immune system . Consequently, HPV infection favors the establishment of an immune tolerogenic environment and the progression of cervical lesions and cancer …”

Expressão de indoleamina 2,3-dioxigenase (IDO) e triptofano 2,3-dioxigenase(TDO) no ambiente cervicovaginal normal, na vaginose bacteriana e nas lesões cervicais associadas ao HPV

“…A manutenção de um microambiente imunossupressor possui um importante papel na carcinogênese de forma geral e também na carcinogênese associada ao HPV (Bashaw et al, 2017). Macrófagos associados a tumores (TAM), linfócitos infiltrantes do tumor (TIL) e neutrófilos associados ao tumor (TAN) são observados em vários tipos de cânceres (Galdiero et al, 2013;Badalamenti et al, 2018).…”

“…Tanto os MDSC da linhagem granulocítica como os TANs ganharam muita relevância mais recentemente e, devido as similaridades de suas características pró-tumorais e fenotípicas, não tem sido simples sua distinção (Bronte et al, 2016;Moses e Brandau, 2016). O epitélio transformado pelo HPV produz fatores solúveis e recruta TAM, TIL e MDSC que foram recentemente identificadas no câncer cervical e associados à expressão de G-CSF do tumor e quimiorresistência (Kawano et al, 2015;Bashaw et al, 2017;Wu et al, 2018). No câncer cervical, os neutrófilos tem sido considerados como tendo atividade pró-tumoral (Punt et al, 2015).…”