Interleukin-27 and IFNγ regulate the expression of CXCL9, CXCL10, and CXCL11 in hepatitis

Basset, Laëtitia; Chevalier, Sylvie; Danger, Yannic; Arshad, Muhammad; Piquet‐Pellorce, Claire; Gascan, Hugues; Samson, Michel

doi:10.1007/s00109-015-1319-6

Cited by 27 publications

(29 citation statements)

References 51 publications

(76 reference statements)

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“…STAT‐1 can also be activated by IL‐27 accompanied with IFN‐γ. Then CXCL9 induced by STAT‐1 finally affects the liver inflammation . In addition, our previous work by Xia et al.…”

Section: Regulation Of Cxcl9mentioning

confidence: 87%

“…STAT-1 can also be activated by IL-27 accompanied with IFN-γ. Then CXCL9 induced by STAT-1 finally affects the liver inflammation [17]. In addition, our previous work by Xia et al identified that HBx protein can induce the CXCL9 transcription by activating NF-κB that binds to its promoter, and CXCL9 promotes the migration of leukocytes in liver with HBV infection [18].…”

Section: Introductionmentioning

confidence: 98%

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CXCL9: evidence and contradictions for its role in tumor progression

et al. 2016

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Chemokines are a group of low molecular weight peptides. Their major function is the recruitment of leukocytes to inflammation sites, but they also play a key role in tumor growth, angiogenesis, and metastasis. In the last few years, accumulated experimental evidence supports that monokine induced by interferon (IFN)‐gamma (CXCL9), a member of CXC chemokine family and known to attract CXCR3‐ (CXCR3‐A and CXCR3‐B) T lymphocytes, is involved in the pathogenesis of a variety of physiologic diseases during their initiation and their maintenance. This review for the first time presents the most comprehensive summary for the role of CXCL9 in different types of tumors, and demonstrates its contradictory role of CXCL9 in tumor progression. Altogether, this is a useful resource for researchers investigating therapeutic opportunities for cancer.

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“…STAT‐1 can also be activated by IL‐27 accompanied with IFN‐γ. Then CXCL9 induced by STAT‐1 finally affects the liver inflammation . In addition, our previous work by Xia et al.…”

Section: Regulation Of Cxcl9mentioning

confidence: 87%

Section: Introductionmentioning

confidence: 98%

CXCL9: evidence and contradictions for its role in tumor progression

et al. 2016

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“…Although these Cancer October 15, 2019 clinical trials still are ongoing and treatment outcome remains unclear, preclinical studies have demonstrated that galunisertib can increase anti-PD-L1 monotherapyelicited intratumor immune-associated gene expression. 24 Pembrolizumab received accelerated approval as a second-line therapy for patients with HCC who developed disease progression while receiving sorafenib based on an international trial with a low percentage of patients from North America (19 of 105 patients). 21 In the current study, we did not observe any obvious correlation between PD-L1-positive tumors and response to PD-1/PD-L1 blockade, 4,13 yet early results have suggested that PD-L1 expression in immune and tumor cells was associated with response to pembrolizumab in a subset of patients with HCC.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the plasma CXCL9 concentration may be altered by other cytokines, including IL-27, which has been reported to regulate CXCL9 expression in patients with hepatitis. 24 Pembrolizumab received accelerated approval as a second-line therapy for patients with HCC who developed disease progression while receiving sorafenib based on an international trial with a low percentage of patients from North America (19 of 105 patients). 13 The current USbased trial supports pembrolizumab as an active agent with manageable toxicity for patients with advanced/metastatic HCC.…”

Section: Discussionmentioning

confidence: 99%

Phase 2 study of pembrolizumab and circulating biomarkers to predict anticancer response in advanced, unresectable hepatocellular carcinoma

Feun

et al. 2019

Cancer

137

108

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BACKGROUND: Checkpoint inhibitors have shown modest activity in patients with advanced hepatocellular carcinoma (HCC). Herein, the authors report a prospective single-institution clinical/translational phase 2 study of pembrolizumab in patients with advanced HCC and circulating biomarkers closely related to response. METHODS: Pembrolizumab was administered at a dose of 200 mg intravenously every 3 weeks among patients who may have developed disease progression while receiving, were intolerant of, or refused sorafenib. The circulating levels of cytokines, chemokines, programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and PD-L2 were correlated with response, tumor PD-L1 expression, and other clinicopathological features. RESULTS: A total of 29 patients were treated and 28 patients were evaluable for response. The most common laboratory grade 3/4 adverse events were increases in aspartate aminotransferase and/or alanine aminotransferase and serum bilirubin, which for the most part were reversible. In terms of efficacy, one patient achieved a complete response and 8 patients achieved partial responses for an overall response rate of 32%. Four other patients had stable disease. The median progression-free survival was 4.5 months and the median overall survival was 13 months. Response did not correlate with prior sorafenib therapy, PD-L1 tumor staining, or a prior history of hepatitis. Correlative studies revealed that high baseline plasma TGF-β levels (≥200 pg/mL) significantly correlated with poor treatment outcomes after pembrolizumab. Tumor PD-L1 and plasma PD-L1/PD-1 levels were associated with plasma IFN-γ or IL-10. CONCLUSIONS: Pembrolizumab was found to demonstrate activity in patients with advanced HCC. Toxicity generally was tolerable and reversible. A set of immunological markers in blood plasma as well as PD-L1 staining indicated that baseline TGF-β could be a predictive biomarker for response to pembrolizumab. Cancer 2019;125:3603-3614.

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“…It is bound by CXCR3, a receptor shared with CXCL4. CXCL9 and CXCL11, which are expressed on CD4 + T cells, CD8 + T cells, NK cells, B cells, and DCs (87,88), are responsible for their recruitment and localization to the lungs.…”

Section: The Important Role Of Chemokines In Lung Carcinomamentioning

confidence: 99%