2016
DOI: 10.1172/jci.insight.86182
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PD-1+ and Foxp3+ T cell reduction correlates with survival of HCC patients after sorafenib therapy

Abstract: BACKGROUND Sorafenib is an oral antiangiogenic agent administered in advanced-stage hepatocellular carcinoma (HCC). Based on preclinical and human studies, we hypothesized that, in addition to its antiangiogenic properties, sorafenib may beneficially reduce the extent of the immunosuppressive network in HCC patients. To test this hypothesis, we examined whether alterations in the immunosuppressive burden of advanced-stage HCC patients correlated with clinical outcome. METHODS In before and after sorafenib tr… Show more

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Cited by 55 publications
(69 citation statements)
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“…Foxp3+ Tregs expressing PD‐1 were also shown to be enriched in human glioblastoma tissue . Expression of PD‐1 on CD8+ T cells and Foxp3+ Tregs is associated with VEGF‐A exposure, and blocking of the VEGF/VEGFR pathway downregulated the frequency of PD‐1 expression on these cells . In the present study, the total number of PD‐1+ cells, including CD8+ T cells and Tregs, was significantly decreased in the effective or refractory Bev group compared with the naïve Bev group.…”
Section: Discussionsupporting
confidence: 48%
“…Foxp3+ Tregs expressing PD‐1 were also shown to be enriched in human glioblastoma tissue . Expression of PD‐1 on CD8+ T cells and Foxp3+ Tregs is associated with VEGF‐A exposure, and blocking of the VEGF/VEGFR pathway downregulated the frequency of PD‐1 expression on these cells . In the present study, the total number of PD‐1+ cells, including CD8+ T cells and Tregs, was significantly decreased in the effective or refractory Bev group compared with the naïve Bev group.…”
Section: Discussionsupporting
confidence: 48%
“…We did not enroll patients with viral‐related HCC and, therefore, it remains unclear that an association between prognosis of HCC and IL‐34 or YKL‐40 is specific for patients with non‐viral HCC. Additionally, the predictive ability of IL‐34 on the prognosis of non‐viral HCC was not compared to other prognostic biomarkers for patients with HCC including microRNA‐128‐3p and Programmed cell death‐1‐positive T cells . The advantages and disadvantages of IL‐34 should be examined in further studies.…”
Section: Discussionmentioning
confidence: 99%
“…Hepatic fibrosis and its biomarkers, such as Wisteria floribunda agglutinin‐positive Mac‐2 binding protein, are risk factors for hepatocarcinogenesis . Many previous reports have identified biomarkers associated with prognosis in HCC . However, limited information is available for biomarkers associated with prognosis of patients with non‐viral HCC.…”
Section: Introductionmentioning
confidence: 99%
“…However, there is also evidence that sorafenib has an immunomodulatory role. For instance, treatment with sorafenib has been shown to improve the immune response by upregulating the activity of tumour‐specific effector T cells, as well as reducing the number of PD‐1 expressing CD8+ T cells and regulatory T cells, which has been correlated with improved OS . In addition to its direct immunomodulatory effect on lymphocytes, sorafenib may also exert an indirect effect on the HCC microenvironment by decreasing the levels of immunosuppressive cytokines such as IL‐10 and TGF‐β1 .…”
Section: Introductionmentioning
confidence: 99%