Serum levels of IL-6 and IL-1β can predict the efficacy of gemcitabine in patients with advanced pancreatic cancer

Mitsunaga, Shuichi; Ikeda, Masafumi; Shimizu, Satoshi; Ohno, Izumi; Furuse, J.; Inagaki, Masumi; Higashi, Sayumi; Kato, Hiroyuki; Terao, Keiji; Ochiai, Atsushi

doi:10.1038/bjc.2013.174

Cited by 136 publications

(114 citation statements)

References 34 publications

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“…In addition to confirming our hypothesis, we observed that LIF titration in serum from PDA patients could have other uses. Indeed, as already reported for IL-6 and IL-11, cytokine serum levels are valuable diagnostic and prognostic tools (47)(48)(49) suggests that the combined detection of LIF and CA19.9 could be greater than CA19.9 alone in the diagnosis of PDA. Finally, LIF titration in serum of PDA patients has a real potent value as a stratifying biomarker of PDA in order to classify PDA patients regarding their possible responsiveness to JAK/STAT targeting agent as Ruxolitinib.…”

Section: Discussionmentioning

confidence: 81%

LIF Drives Neural Remodeling in Pancreatic Cancer and Offers a New Candidate Biomarker

et al. 2018

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Abstract:Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive stroma and pathogenic modifications to the peripheral nervous system that elevate metastatic capacity. In this study, we show that the IL-6-related stem cell promoting factor LIF supports PDACassociated neural remodeling (PANR). LIF was overexpressed in tumor tissue compared to healthy pancreas, but its receptors LIFR and gp130 were expressed only in intratumoral Significance:This study suggests a target to limit neural remodeling in pancreatic cancer, which contributes to poorer quality of life and heightened metastatic progression in patients.

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Section: Discussionmentioning

confidence: 81%

LIF Drives Neural Remodeling in Pancreatic Cancer and Offers a New Candidate Biomarker

et al. 2018

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“…This cytokine plays a key role in the early growth, maintenance, and metastasis of PDAC tumors (27, 28). Previous studies in either mixed cohorts of patients with resectable and unresectable disease (36, 37) or in those undergoing gemcitabine based therapy (38) have found a negative correlation between IL-6 and clinical outcome. In agreement with these reports, our study found that IL-6 plasma levels in treatment naïve patients were significantly negatively associated OS.…”

Section: Discussionmentioning

confidence: 96%

Systemic Immune Activity Predicts Overall Survival in Treatment-Naïve Patients with Metastatic Pancreatic Cancer

Farren

Mace

Geyer

et al. 2016

Clinical Cancer Research

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Purpose: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a 5-year survival rate <7% and is ultimately refractory to most treatments. To date, an assessment of immunologic factors relevant to disease has not been comprehensively performed for treatment-na€ ve patients. We hypothesized that systemic immunologic biomarkers could predict overall survival (OS) in treatment-na€ ve PDAC patients.Experimental Design: Peripheral blood was collected from 73 patients presenting with previously untreated metastatic PDAC. Extensive immunologic profiling was conducted to assess relationships between OS and the level of soluble plasma biomarkers or detailed immune cell phenotypes as measured by flow cytometry.Results: Higher baseline levels of the immunosuppressive cytokines IL6 and IL10 were strongly associated with poorer OS (P ¼ 0.008 and 0.026, respectively; HR ¼ 1.16 and 1.28, respectively), whereas higher levels of the monocyte chemoattractant MCP-1 were associated with significantly longer OS Conclusions: These data support the hypothesis that baseline immune status predicts PDAC disease course and overall patient survival. To our knowledge, this work represents the largest cohort and most comprehensive immune profiling of treatment-na€ ve metastatic PDAC patients to date.

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“…Therefore, improving the immune status of cancer patients is required for effective cancer immunotherapies. Prospective and retrospective studies have shown that serum IL-6 levels are related to tumor stage and size, metastasis, survival of colon cancer patients [19], chemotherapy efficacy for advanced pancreatic cancer [20], advanced stage and metastasis-related morbidity of breast cancer [21], and the efficacy of personalized peptide vaccination for advanced biliary tract cancer [22]. Results from these studies suggest that IL-6 levels in cancer are not simply useful as promising prognostic biomarkers, but are also related to tumorigenesis and anti-tumor immune responses.…”

Section: Discussionmentioning

confidence: 99%

IL-6 down-regulates HLA class II expression and IL-12 production of human dendritic cells to impair activation of antigen-specific CD4+ T cells

Ohno

Kitamura

Takahashi

et al. 2016

Cancer Immunol Immunother

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Immunosuppression in tumor microenvironments critically affects the success of cancer immunotherapy. Here, we focused on the role of interleukin (IL)-6/signal transducer and activator of transcription (STAT3) signaling cascade in immune regulation by human dendritic cells (DCs). IL-6-conditioned monocyte-derived DCs (MoDCs) impaired the presenting ability of cancer-related antigens. Interferon (IFN)-γ production attenuated by CD4+ T cells co-cultured with IL-6-conditioned MoDCs corresponded with decreased DC IL-12p70 production. Human leukocyte antigen (HLA)-DR and CD86 expression was significantly reduced in CD11b+CD11c+ cells obtained from peripheral blood mononuclear cells (PBMCs) of healthy donors by IL-6 treatment and was STAT3 dependent. Arginase-1 (ARG1), lysosomal protease, cathepsin L (CTSL), and cyclooxygenase-2 (COX2) were involved in the reduction of surface HLA-DR expression. Gene expressions of ARG1, CTSL, COX2, and IL6 were higher in tumor-infiltrating CD11b+CD11c+ cells compared with PBMCs isolated from colorectal cancer patients. Expression of surface HLA-DR and CD86 on CD11b+CD11c+ cells was down-regulated, and T cell-stimulating ability was attenuated compared with PBMCs, suggesting that an immunosuppressive phenotype might be induced by IL-6, ARG1, CTSL, and COX2 in tumor sites of colorectal cancer patients. There was a relationship between HLA-DR expression levels in tumor tissues and the size of CD4+ T and CD8+ T cell compartments. Our findings indicate that IL-6 causes a dysfunction in human DCs that activates cancer antigen-specific Th cells, suggesting that blocking the IL-6/STAT3 signaling pathway might be a promising strategy to improve cancer immunotherapy

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Serum levels of IL-6 and IL-1β can predict the efficacy of gemcitabine in patients with advanced pancreatic cancer

Cited by 136 publications

References 34 publications

LIF Drives Neural Remodeling in Pancreatic Cancer and Offers a New Candidate Biomarker

LIF Drives Neural Remodeling in Pancreatic Cancer and Offers a New Candidate Biomarker

Systemic Immune Activity Predicts Overall Survival in Treatment-Naïve Patients with Metastatic Pancreatic Cancer

IL-6 down-regulates HLA class II expression and IL-12 production of human dendritic cells to impair activation of antigen-specific CD4+ T cells

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