Correlation of T-helper secretory differentiation and types of antigen-presenting cells in squamous intraepithelial lesions of the uterine cervix

Al-Saleh, Walid; Giannini, Sandra L.; Jacobs, Nathalie; Moutschen, Michel; Doyen, Jean; Boniver, Jacques; Delvenne, Philippe

doi:10.1002/(sici)1096-9896(199803)184:3<283::aid-path25>3.0.co;2-k

Cited by 95 publications

(76 citation statements)

References 40 publications

(34 reference statements)

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“…A number of recent publications has drawn attention to tumorinduced dysfunction of DC as a mechanism to escape immunosurveillance (3)(4)(5)(6)(7)(8)(9). Indeed, a reduced number of DC in primary tumors has been observed for breast cancer, basal cell skin cancer, cervical cancer, and colon cancer, among others (10). In addition, advanced cancer is associated with impaired differentiation and Ag-presenting functions of DC and their precursor cells (11).…”

Section: T He Importance Of Dendritic Cells (Dc) 2 In the Inductionmentioning

confidence: 97%

Prostanoids Play a Major Role in the Primary Tumor-Induced Inhibition of Dendritic Cell Differentiation

Sombroek¹,

Stam²,

Masterson³

et al. 2002

The Journal of Immunology

185

110

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Production of immunosuppressive factors is one of the mechanisms by which tumors evade immunosurveillance. Soluble factors hampering dendritic cell (DC) development have recently been identified in culture supernatants derived from tumor cell lines. In this study, we investigated the presence of such factors in 24-h culture supernatants from freshly excised solid human tumors (colon, breast, renal cell carcinoma, and melanoma). While primary tumor-derived supernatant (TDSN) profoundly hampered the in vitro DC differentiation from CD14+ plastic-adherent monocytes or CD34+ precursors (based on morphology and CD1a/CD14 phenotype), the effects of tested tumor cell line-derived supernatants were minor. Cyclooxygenase (COX)-1- and COX-2-regulated prostanoids present in the primary TDSN were found to be solely responsible for the observed hampered differentiation of monocyte-derived DC (MoDC). In contrast, both prostanoids and IL-6 were found to contribute to the TDSN-induced inhibition of DC differentiation from CD34+ precursor cells. While the addition of TDSN during differentiation interfered with the ability of CD34-derived DC to stimulate a primary allogeneic T cell response, it actually increased this ability of MoDC. These opposite effects were correlated to different effects of the TDSN on the expression levels of CD86 and HLA-DR on the DC from the different precursor origins. Although TDSN increased the T cell-stimulatory capacity of MoDC, TDSN inhibited the IL-12 production and increased the IL-10 production of MoDC, thus skewing them to a type-2 T cell-inducing phenotype. In conclusion, this study demonstrates that primary tumors negatively impact DC development and function through COX-1 and -2 regulated factors, whereas tumor-derived cell lines may lose this ability upon in vitro propagation.

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Section: T He Importance Of Dendritic Cells (Dc) 2 In the Inductionmentioning

confidence: 97%

Prostanoids Play a Major Role in the Primary Tumor-Induced Inhibition of Dendritic Cell Differentiation

Sombroek¹,

Stam²,

Masterson³

et al. 2002

The Journal of Immunology

185

110

View full text Add to dashboard Cite

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“…6,17,18 For example, we have observed that the density of LC is significantly reduced and the immunosuppressive cytokine IL10 is more frequently expressed in the microenvironment of TZ in comparison to the exocervix. 5,6,17 To the contrary, other groups have reported that the density of LC in the TZ is equal to that of the exocervix. 19,20 As an approach to understanding the factors involved in the initiation and progression of SILs, we sought to use a variety of methods to assess the differential density and the antigen presenting function of LC derived from TZ and SILs.…”

mentioning

confidence: 88%

Influence of the mucosal epithelium microenvironment on Langerhans cells: Implications for the development of squamous intraepithelial lesions of the cervix

Giannini

Hubert

Doyen

et al. 2001

Intl Journal of Cancer

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101

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We have addressed the notion that the initiation and progression of human papillomavirus associated cancer of the uterine cervix are associated with alterations of Langerhans cells (LC) within the mucosal squamous epithelium. Since the transformation zone (TZ) of the cervix is the site where the majority of squamous intraepithelial lesions (SIL) are initiated, in contrast to the exocervix, we decided to investigate the influence of the local microenvironment within the TZ on the function and density of LC. We show that the TZ is associated with a significant reduction in the density of immature LC (CD1a/LAG) compared to the exocervix. In contrast, the development of SILs is attributed with a relative increased density of immature LC, compared to the TZ. Furthermore, we show that this variability in LC density is correlated with a differential expression of TNF␣ and MIP3␣ within the micro-environment of the TZ and SILs. Both TZ and SIL epithelium-derived LC, in the presence of allogeneic PBMC, induced lower levels of proliferation and IL2 production and higher levels of the immunosuppressive cytokine IL10 in comparison to the exocervix. Nevertheless, the epithelium-derived LC in SILs exhibits a reduction in their functional activity, relative to the TZ. Together our studies suggest that the immunosurveillance within the epithelium of the TZ may be intrinsically perturbed due to the altered expression of chemokines/cytokines and the concomitant diminished density of LC. Furthermore, following HPV infection and the development of SILs, the function of LC may be further incapacitated by viral associated mechanisms. © 2002 Wiley-Liss, Inc. Key words: Langerhans cells (LC); transformation zone (TZ); squamous intraepithelial lesions (SILs); human papillomavirus (HPV); local immunityThe chronic infection of keratinocytes of the uterine cervix by the human papillomavirus (HPV) is associated with the development of cervical cancer. Despite the evidence that HPV is strongly implicated as the causative agent in the etiology of cervical cancer and its precursors (SIL, squamous intraepithelial lesion), HPV infection alone is not sufficient for cancer development. 1 The role of the intrinsic immunity in controlling HPV infection and the subsequent development of SILs is shown indirectly by the increased frequency of HPV-associated lesions in patients with depressed cell-mediated immunity. 2,3 For the most part, the development of SIL and/or cervical cancer is preferentially associated with a local type II (IL4/IL6) and/or immunosuppressive (IL 10) cytokine pattern, 4 -7 not a cell-mediated type I immune response, which is more appropriate for tumor immunity. Given that immune responses in mucosal sites are frequently dominated by a "default" type 2 response, 8,9 it is essential to consider mechanisms that contribute to this predisposition in order to design vaccine strategies to promote a localized cell-mediated immunity.The squamous epithelium of the cervix is composed mainly of keratinocytes, the primary target of HPV and a ...

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“…For example, previous works have demonstrated that metaplastic areas are associated with a lower density of LCs. 9,10 Besides the communication of epithelial and immune cells by soluble factors, there also exist important cell-cell interactions. For example, the protein E-cadherin, which is critical for intercellular adhesiveness and maintenance of normal epithelial tissue architecture, is also involved in the homophilic and heterotypic interactions between epithelial cells and diverse cell types of the immune response, including LCs 11 and intraepithelial T lymphocytes (via ␣E␤7 integrin).…”

mentioning

confidence: 99%

Transforming Growth Factor-β1-Mediated Slug and Snail Transcription Factor Up-Regulation Reduces the Density of Langerhans Cells in Epithelial Metaplasia by Affecting E-Cadherin Expression

Herfs

Hubert

Kholod

et al. 2008

The American Journal of Pathology

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Epithelial metaplasia (EpM) is an acquired tissue abnormality resulting from the transformation of epithelium into another tissue with a different structure and function. This adaptative process is associated with an increased frequency of (pre)cancerous lesions. We propose that EpM is involved in cancer development by altering the expression of adhesion molecules important for cell-mediated antitumor immunity. Langerhans cells (LCs) are intraepithelial dendritic cells that initiate immune responses against viral or tumor antigens on both skin and mucosal surfaces. In the present study, we showed by immunohistology that the density of CD1a ؉ LCs is reduced

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Correlation of T-helper secretory differentiation and types of antigen-presenting cells in squamous intraepithelial lesions of the uterine cervix

Cited by 95 publications

References 40 publications

Prostanoids Play a Major Role in the Primary Tumor-Induced Inhibition of Dendritic Cell Differentiation

Prostanoids Play a Major Role in the Primary Tumor-Induced Inhibition of Dendritic Cell Differentiation

Influence of the mucosal epithelium microenvironment on Langerhans cells: Implications for the development of squamous intraepithelial lesions of the cervix

Transforming Growth Factor-β1-Mediated Slug and Snail Transcription Factor Up-Regulation Reduces the Density of Langerhans Cells in Epithelial Metaplasia by Affecting E-Cadherin Expression

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