Interleukin-10 is a growth factor for human melanoma cells and down-regulates HLA class-I, HLA class-II and ICAM-1 molecules

Yue, Feng Yun; Dummer, Reinhard; Geertsen, Ralf; Hofbauer, Günther F.L.; Laine, Elisabeth; Manolio, Silvana; Burg, Günter

doi:10.1002/(sici)1097-0215(19970516)71:4<630::aid-ijc20>3.0.co;2-e

Cited by 219 publications

(104 citation statements)

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“…IL-10 may down-regulate MHC class I and class II expression, impeding both CTL and antibody responses, but may enhance natural killer cell activity. [6][7][8][9][10][11][12] Strong anti-HCV-specific T-helper response may contribute to self-limiting HCV infection and sustained response to interferon therapy, 30,[34][35][36][37][38] and similar effects can be attributed to HCV-specific CTL response. 30 NOTE.…”

Section: Discussionmentioning

confidence: 99%

“…For example, interleukin 10 (IL-10) is a potent anti-inflammatory Th2 cytokine that down-regulates the expression of major histocompatibility complex (MHC) class I and class II molecules as well as the production of Th1 cytokines. [6][7][8][9][10][11][12] IL-10 levels differ widely between individuals, possibly because of polymorphisms in the promoter region of the IL-10 gene. 13,14 Specifically, 3 single nucleotide polymorphisms (SNPs) in the promoter (at positions Ϫ1082, Ϫ819, and Ϫ592 relative to the transcription start site) 15 form 3 SNP combinations (ATA, ACC, GCC) associated with differential IL-10 expression.…”

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confidence: 99%

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Interleukin 10 polymorphisms as predictors of sustained response in antiviral therapy for chronic hepatitis C infection

et al. 2001

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Host genetic factors have been reported to influence the natural history of hepatitis C virus (HCV) infection. We examined whether variation in interleukin 10 (IL-10) and tumor necrosis factor ␣ (TNF-␣) genes would predict the likelihood of sustained response to antiviral therapy. Single nucleotide polymorphisms (SNPs) and microsatellites at two loci encoding the cytokines IL-10 and TNF-␣ were determined by polymerase chain reaction (PCR)-based techniques. Their relationship to the outcome of antiviral therapy for chronic HCV infection was studied in 49 white patients who had a virologically sustained response (SR) and in 55 white nonresponders (NR) to a combination of interferon alfa-2b and ribavirin (IFN ؉ R). Several IL-10 variants were more frequent among SRs compared with NRs. Carriage of the ؊592A or the ؊819T SNP was associated with SR (odds ratio [OR] ‫؍‬ 2.2; P ‫؍‬ .016). The ؊592A/A and the exclusively linked ؊819T/T genotypes were also associated with SR (OR ‫؍‬ 16.6; P ‫؍‬ .013 for either). The haplotype consisting of the 108-bp IL-10.R microsatellite and ؊3575T, ؊2763C, ؊1082A, ؊819T, ؊592A was also associated with SR (OR ‫؍‬ 2.65; P ‫؍‬ .01). Stratification for viral genotype, baseline viral RNA concentration, and histologic status identified homozygosity for the haplotype as the principal determinant: all 5 homozygous individuals achieved SR (OR crude ‫؍‬ 13.7; P ‫؍‬ .025; stratified ORs ‫؍‬ 1.9-7.0), whereas heterozygotes differed only slightly from wild-type carriers. In contrast, TNF alleles defined by promoter sequences ؊238G/A and ؊308G/A were approximately equally distributed among SR and NR. In conclusion, homozygosity for ؊592A, ؊819T or the extended haplotype (108bp) ؊ ( During the last decade, treatment for hepatitis C virus (HCV) infection has rapidly improved. Interferon alfa-2b in combination with ribavirin (IFN ϩ R) has become the standard regimen for HCV infection. Sustained response (SR) to IFN ϩ R, defined as undetectable HCV RNA at 6 months after discontinuation of therapy, is achievable in 30% to 60% of treated patients.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Interleukin 10 polymorphisms as predictors of sustained response in antiviral therapy for chronic hepatitis C infection

et al. 2001

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“…However, in most cases, it has been obvious that advanced and/or poorly immunogenic tumors are refractory to immunotherapy possibly because of immunosuppressive effects in cancer patients, limited identification of cancer-specific antigens and possibly some tumor-regulated resistance mechanisms against immune effector cells such as expression of FAS ligand or down-regulation of tumor-specific MHC antigens. 20,21 It is well accepted that DC are potent professional APC with the capability of inducing tumor-specific CTL activity and strong antitumor effects. In addition, it has been shown that DC pulsed with tumor-derived antigens including whole cell lysates, RNA and apoptotic bodies can trigger tumor-specific responses.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of antitumor immunity against B16 melanoma tumor using genetically modified dendritic cells to produce cytokines

Akiyama¹,

Watanabe

Maruyama³

et al. 2000

Gene Ther

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Dendritic cells (DC) that have been genetically modified to express cytokine genes may be novel tools for inducing antitumor immune responses. In the present study, the pMX retroviral vector was modified to express the mouse IL-2 (mIL-2pMX) and mouse IL-12 (mIL-12pMX) genes. Supernatants from 293 cells transfected with pMX retroviral vectors were harvested and used to transduce mouse lin − bone marrow (BM) progenitor cells. After 48 h co-culture with pseudotype retrovirus, BM cells were cultured for 12 days in the presence of mGM-CSF, mSCF and mTNF-␣ to obtain a DC-enriched fraction. Flow cytometric analysis showed that GFP protein expression in these cultures was 20-40% and that 40-50% of the cultured BM cells were positive for the DC marker, DEC205. About 60% of cells sorted for DEC205 also expressed GFP. The supernatants of DC-mIL-2 and DC-mIL-12 cultured for 48 h contained 5.2 ± 0.15 and 33.9

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“…T cell activity can be directly inhibited by immunosuppressive factors, such as IL-10, that are secreted either by the tumor (43,44) (49,50). In contrast to these well-characterized mechanisms to evade Ag presentation to CD8 ϩ T cells, there exist few examples by which tumor cells or viruses interfere with MHC class II Ag presentation.…”

Section: Discussionmentioning

confidence: 99%

A Tumor-Associated Glycoprotein That Blocks MHC Class II-Dependent Antigen Presentation by Dendritic Cells

Gutzmer¹,

Li²,

Sutterwala

et al. 2004

The Journal of Immunology

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Tumors evade immune surveillance despite the frequent expression of tumor-associated Ags (TAA). Tumor cells escape recognition by CD8+ T cells through several mechanisms, including down-regulation of MHC class I molecules and associated Ag-processing machinery. However, although it is well accepted that optimal anti-tumor immune responses require tumor-reactive CD4+ T cells, few studies have addressed how tumor cells evade CD4+ T cell recognition. In this study, we show that a common TAA, GA733-2, and its murine orthologue, mouse epithelial glycoprotein (mEGP), function in blocking MHC class II-restricted Ag presentation by dendritic cells. GA733-2 is a common TAA that is expressed normally at low levels by some epithelial tissues and a subset of dendritic cells, but at high levels on colon, breast, lung, and some nonepithelial tumors. We show that ectopic expression of mEGP or GA733-2, respectively, in dendritic cells derived from murine bone marrow or human monocytes results in a dose-dependent inability to stimulate proliferation of Ag-specific or alloreactive CD4+ T cells. Dendritic cells exposed to cell debris from tumors expressing mEGP are similarly compromised. Furthermore, mice immunized with dendritic cells expressing mEGP from a recombinant adenovirus vector exhibited a muted anti-adenovirus immune response. The inhibitory effect of mEGP was not due to down-regulation of functional MHC class II molecules or active suppression of T cells, and did not extend to T cell responses to superantigen. These results demonstrate a novel mechanism by which tumors may evade CD4+ T cell-dependent immune responses through expression of a TAA.

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Interleukin-10 is a growth factor for human melanoma cells and down-regulates HLA class-I, HLA class-II and ICAM-1 molecules

Cited by 219 publications

References 28 publications

Interleukin 10 polymorphisms as predictors of sustained response in antiviral therapy for chronic hepatitis C infection

Interleukin 10 polymorphisms as predictors of sustained response in antiviral therapy for chronic hepatitis C infection

Enhancement of antitumor immunity against B16 melanoma tumor using genetically modified dendritic cells to produce cytokines

A Tumor-Associated Glycoprotein That Blocks MHC Class II-Dependent Antigen Presentation by Dendritic Cells

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