Low Expression of Human Histocompatibility Soluble Leukocyte Antigen-G (HLA-G5) in Invasive Cervical Cancer With and Without Metastasis, Associated With Papilloma Virus (HPV)

Guimarães, M; Soares, Christiane Pienna; Donadi, Eduardo Antônio; Derchain, Sophie; Andrade, Liliana Aparecida Lucci De Angelo; Silva, Tarsia G.A.; Hassumi, Marcela K.; Simões, Renata Toscano; Miranda, Fabiana Alves; Lira, Régia Caroline Peixoto; Crispim, Janaína Oliveira; Soares, Edson García

doi:10.1369/jhc.2009.954131

Cited by 34 publications

(35 citation statements)

References 35 publications

(50 reference statements)

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“…In another study, Goncalves et al [57] reported similar results: HLA-G5 isoform molecules were detected by immunohistochemistry in 25 cases of 74 cervical cancer biopsies (31.6%), 17 (32.7%) without metastasis and 8 (29.6%) with metastasis. Moreover, a low expression of the HLA-G5 isoform was observed in the majority of HPV-related cases [58] . In this report the authors suggest that HPV may be involved in the modulation of HLA-G surface expression by using similar mechanisms to those observed in HLA class I downregulation by HPV oncoproteins; however, it is well-known that the HLA-G-immunosuppressive effect is mediated by upregulation of this molecule.…”

Section: Discussionmentioning

confidence: 97%

Altered HLA Class I and HLA-G Expression Is Associated with IL-10 Expression in Patients with Cervical Cancer

Rodríguez¹,

Galeano²,

Palacios

et al. 2011

Pathobiology

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Although high-risk human papillomaviruses (HPVs) are an important risk factor in the etiopathogenesis of cervical cancer, increasing evidence suggests that the ability to avoid immune surveillance seems to be linked to the transforming potential of HPV and a rapid progression to cancer. In other cancer models, IL-10 contributes to impair anti-tumor immune response either by downregulating human leukocyte antigen Class I (HLA-I) expression or by increasing HLA-G expression. To comprehend how these alterations could contribute to evasion of immune surveillance in cervical cancer, we analyzed HLA-I, HLA-G and IL-10 expressions by immunohistochemistry in 63 biopsies from patients with cervical intraepithelial neoplasia III (CIN-III) and cervical cancer. Immunohistochemistry showed absent or weak HLA-I expression in 50/59 cases. In these cases, a high percentage had loss of heterozygosis. IL-10 and HLA-G expression were observed in 46.6 and 27.6% of cases, respectively. Concurrent upregulation of IL-10 was found in 87.5% of HLA-G positive cases (p = 0.000). Similarly, a significant association between IL-10 expression and HLA-I downregulation was found (p = 0.028). Finally, we observed higher HLA-G expression in patients with HLA-I downregulation than in those with normal HLA-I expression (p = 0.004). Our results suggest that, in cervical cancer, the IL-10 expression may induce an immunosuppressive environment by upregulating HLA-G expression and downregulating HLA class I expression.

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Section: Discussionmentioning

confidence: 97%

Altered HLA Class I and HLA-G Expression Is Associated with IL-10 Expression in Patients with Cervical Cancer

Rodríguez¹,

Galeano²,

Palacios

et al. 2011

Pathobiology

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“…13 On the other hand, Zheng et al reported that HLA-G is abundantly expressed in premalignant and malignant cervical intraepithelial lesions. 5 Thus, our study found that HLA-G expression was a significant predictor in relation to CIN I and age, such that overall, HLA-G was present in approximately 75.86% of the cases and was primarily detected in epithelial cells, fibroblasts and lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Greater expression of the human leukocyte antigen-G (HLA-G) and interleukin-17 (IL-17) in cervical intraepithelial neoplasia: analytical cross-sectional study

et al. 2014

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CONTEXT AND OBJECTIVE: Impaired local cell immunity seems to contribute towards the pathogenesis and progression of cervical intraepithelial neoplasia (CIN), but the underlying molecular mechanisms promoting its progression remain unclear. Identification of new molecular markers for prognosis and diagnosis of early-stage CIN may aid in decreasing the numbers of CIN cases. Several novel immunoregulatory molecules have been discovered over the past few years, including the human leukocyte antigen G (HLA-G), which through interaction with its receptors exerts important tolerogenic functions. Several lines of evidence suggest that T-helper interleukin-17 (IL-17)-producing cells (Th17 cells) may play a role in antitumor immunity. However, recent reports have implicated Th17 cells and their cytokines in both pro and anti-tumorigenic processes. The aim of the study was to evaluate the roles of HLA-G and Th17 in the immunopathogenesis of CIN I. DESIGN AND SETTING: Analytical cross-sectional study with a control group using 58 cervical specimens from the files of a public university hospital providing tertiary-level care. METHODS:We examined HLA-G and IL-17 expression in the cervical microenvironment by means of immunohistochemistry, and correlated these findings with clinical and pathological features. RESULTS: There was a greater tendency towards HLA-G and IL-17 expression in specimens that showed CIN I, thus suggesting that these molecules have a contribution towards cervical progression. CONCLUSION: These findings suggest that HLA-G and IL-17 expression may be an early marker for assessing the progression of cervical lesions. RESUMO CONTEXTO E OBJETIVO:A deficiência na imunidade celular localizada parece contribuir para a patogênese e progressão das neoplasias intraepiteliais cervicais (NIC), no entanto, ainda não está totalmente esclarecido o mecanismo molecular fundamental nesse processo de progressão. A identificação de novos marcadores moleculares de prognóstico e diagnóstico das NIC em estágios precoces pode ajudar a diminuir a quantidade de casos de NIC. Várias novas moléculas com função imunorregulatória foram descobertas nos últimos anos, inclusive o antígeno leucocitário humano G (HLA-G), que, através de interação com os receptores, tem importantes funções tolerogênicas. Diversas linhas de evidência sugerem que as células T-ajudantes produtoras de interleucina-17 (IL-17, células Th17), podem desempenhar um papel na imunidade antitumoral. Porém, recentes relatos implicaram as células Th17 e suas citocinas tanto em processos pro-quanto anti-tumorigênicos. O objetivo do estudo foi avaliar o papel do HLA-G e Th17 na imunopatogênese das NIC I. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico com grupo controle em 58 espécimes cervicais dos arquivos de um hospital universitário público com assistência prestada no nível terciário. MÉTODOS: Avaliamos a expressão de HLA-G e IL-17 por imunoistoquímica no microambiente cervical, associando esses achados com as características clínico-patológicas. RESULTADOS...

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“…If we used the staining evaluation method in that study (0-25% as negative), HLA-G expression in cervical cancer samples was 58.1% (75/129). Using the specific mAb 5A6G7 for the HLA-G5 isoform, Guimarães et al [28] found that HLA-G5 molecules were detected in 31.6% (25/79) patients and no HLA-G5 staining was observed in normal cervical specimens. These studies showed that HLA-G expression is negative in normal cervical tissues.…”

Section: Discussionmentioning

confidence: 99%

Human leukocyte antigen-G (HLA-G) expression in cervical cancer lesions is associated with disease progression

Zhang²,

Lin³

et al. 2012

Human Immunology

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Low Expression of Human Histocompatibility Soluble Leukocyte Antigen-G (HLA-G5) in Invasive Cervical Cancer With and Without Metastasis, Associated With Papilloma Virus (HPV)

Cited by 34 publications

References 35 publications

Altered HLA Class I and HLA-G Expression Is Associated with IL-10 Expression in Patients with Cervical Cancer

Altered HLA Class I and HLA-G Expression Is Associated with IL-10 Expression in Patients with Cervical Cancer

Greater expression of the human leukocyte antigen-G (HLA-G) and interleukin-17 (IL-17) in cervical intraepithelial neoplasia: analytical cross-sectional study

Human leukocyte antigen-G (HLA-G) expression in cervical cancer lesions is associated with disease progression

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