IFN-gamma regulates the expression of B7-H1 in dermal fibroblast cells

Lee, Sangkeun; Seo, Sam-Hwa; Kim, Byoungsoo; Kim, Chang Deok; Lee, Jeung‐Hoon; Kang, Jung-Soo; Maeng, Pil Jae; Lim, Jong-Soon

doi:10.1016/j.jdermsci.2005.06.008

Cited by 114 publications

(107 citation statements)

References 30 publications

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“…15,41 In our immunohistochemical analysis mean intraepithelial PD-L1+ tumor-infiltrating lymphocytes were higher in medullary carcinoma compared with microsatellite unstable and microsatellite stable colorectal carcinomas. In normal physiology, PD-L1 expression can be induced by IFNγ as a means to protect tissues from infection-induced immune-mediated damage, 42,43 but in tumors enriched with an IFNγ microenvironment, such as microsatellite unstable tumors, the same mechanism may possibly be exploited as a means of antitumor immune escape. There is also evidence that PD-L1 expression can be driven by oncogenic signaling pathways as is the case with PTEN deletion in glioblastomas 44 and constitutive anaplastic lymphoma kinase signaling in lung cancers, which drive PD-L1 expression through signal transducer and activator 3 (STAT3) signaling.…”

Section: Discussionmentioning

confidence: 99%

Medullary carcinoma of the colon: a distinct morphology reveals a distinctive immunoregulatory microenvironment

Friedman

Brodsky

et al. 2016

Modern Pathology

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Medullary carcinoma of the colon is a unique histologic subtype of microsatellite unstable colorectal carcinoma but little is known regarding its tumor-immunoregulatory microenvironment. The aims of this study were to characterize the immune environment of medullary carcinoma and compare it with other microsatellite unstable and microsatellite stable colorectal carcinomas. An initial gene expression microarray analysis of six cases of medullary carcinoma was used to detect potentially differentially expressed genes. We extended this analysis utilizing genomic data from the Cancer Genome Atlas to compare eight cases of medullary carcinoma with other microsatellite unstable and stable carcinomas. Finally, we evaluated expression of key immune pathway proteins and lymphocyte subsets via immunohistochemistry of a large group of medullary carcinomas (n = 105) and compared these findings with three other groups: poorly differentiated, microsatellite unstable well-differentiated and microsatellite stable well-differentiated carcinomas. Microarray and the Cancer Genome Atlas data analysis identified significant upregulation of several immunoregulatory genes induced by IFNγ including IDO-1, WARS (tRNA(trp)), GBP1, GBP4, GBP5, PDCD1 (PD-1), and CD274 (PD-L1) in medullary carcinoma compared with other microsatellite unstable and microsatellite stable tumors. By immunohistochemistry, IDO-1 was expressed in 64% of medullary carcinomas compared with 19% (9/47) of poorly differentiated carcinomas, 14% (3/22) of microsatellite unstable, and 7% (2/30) of the microsatellite stable well-differentiated carcinomas (Po 0.0001). tRNA(trp) was overexpressed in 81% (84/104) of medullary carcinomas, 19% (9/47) of poorly differentiated, 32% (7/22) of microsatellite unstable, and 3% (1/30) of microsatellite stable well-differentiated carcinomas (Po 0.0001). Medullary carcinoma had higher mean CD8+ and PD-L1+ tumor-infiltrating lymphocytes compared with all other groups (P o0.0001). This study demonstrates overexpression of several immunoregulatory genes in microsatellite unstable colorectal carcinomas and that expression of these genes and proteins is more prevalent in the medullary carcinoma subtype, which may be of use both diagnostically and therapeutically.

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Section: Discussionmentioning

confidence: 99%

Medullary carcinoma of the colon: a distinct morphology reveals a distinctive immunoregulatory microenvironment

Friedman

Brodsky

et al. 2016

Modern Pathology

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“…16 Cytokines, especially interferon-gamma (IFNg), that are expressed by activated T cells can induce PD-L1 expression in the surrounding tumor cells via specific signaling pathways. [17][18][19] To better elucidate the correlation between PD-L1 expression and TILs in PeSCC, the mRNA expression levels of PD-L1, IFNg, and CD8 C were evaluated in 24 primary penile cancer specimens. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed a significant positive correlation between PD-L1 and IFNg or CD8 C ( Fig.…”

Section: Correlation Between Pd-l1 Expression and Ifng In Pesccmentioning

confidence: 99%

Tumor PD-L1 expression is correlated with increased TILs and poor prognosis in penile squamous cell carcinoma

Deng

Guo

et al. 2017

OncoImmunology

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Despite its rare incidence worldwide, penile squamous cell carcinoma (PeSCC) still presents with significant morbidity and mortality due to the limited treatment options for advanced patients, especially those in developing countries. The program death-1 (PD-1)/PD-1 ligand (PD-L1) axis has been demonstrated to play an important role in tumor immune escape, and immunotherapies targeting this pathway have shown great success in certain cancer types. Here, we analyzed the expression pattern of PD-L1 in tumor cells and tumorinfiltrating lymphocytes (TILs) in PeSCC with a multi-center cohort. We found that the majority of PeSCCs (53.4%) were PD-L1-positive and that high PD-L1 expression in tumor cells was associated with a poor prognosis. Notably, PD-L1 expression in tumor cells was significantly associated with the extent of TILs and CD8 C TILs. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) showed that PD-L1 was positively correlated with interferon-gamma (IFNg) and CD8 C gene expression. Moreover, we defined the constitutive and inducible surface expression of PD-L1 in newly established primary PeSCC cell lines. Interestingly, two PeSCC cell lines had high intrinsic PD-L1 expression. Another cell line showed low PD-L1 expression, but the PD-L1 expression could be induced by IFNg stimulation. Overall, our data showed that high PD-L1 expression in penile tumor cells indicated a poor prognosis. The upregulation of PD-L1 in PeSCC included both extrinsic and intrinsic mechanisms. These findings indicated that the PD-1/PD-L1 axis might be a potential therapeutic target for patients with penile squamous cell carcinoma.

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“…To further explore the possible mechanism of IL-12 exerts function in regulating B7-H1 expression; we investigated the expression of IFN-γ firstly, because IFN-γ has been well known to induce the expression of B7-H1 (Lee et al, 2005;Lee et al, 2006;Kondo et al, 2010). It was found that rIL-12 and Ad-IL-12-GFP treated groups produced a higher level of IFN-γ in the supernatants of monocyte-derived macrophages cocultured with SKOV3 system.…”

Section: Il-12 Increased the Level Of Ifn-γ And Decreased The Level Omentioning

confidence: 99%

IL-12 Regulates B7-H1 Expression in Ovarian Cancer-associated Macrophages by Effects on NF-κB Signalling

Xiong¹,

Ma²,

Wu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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IFN-gamma regulates the expression of B7-H1 in dermal fibroblast cells

Cited by 114 publications

References 30 publications

Medullary carcinoma of the colon: a distinct morphology reveals a distinctive immunoregulatory microenvironment

Medullary carcinoma of the colon: a distinct morphology reveals a distinctive immunoregulatory microenvironment

Tumor PD-L1 expression is correlated with increased TILs and poor prognosis in penile squamous cell carcinoma

IL-12 Regulates B7-H1 Expression in Ovarian Cancer-associated Macrophages by Effects on NF-κB Signalling

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