Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

Torres, Carolina; Linares, Ana María; Alejandre, M.J.; Palomino-Morales, Rogelio; Caba, Octavio; Prados, José Luis Paniza; Aránega, Amelia; Delgado, Juan Ramón; Irigoyen, A.; Martínez-Galán, Joaquina; Guzman, Francisco M. Ortuño; Rojas, Ignacio; Perales, Sonia

doi:10.1155/2015/518284

Cited by 20 publications

(15 citation statements)

References 61 publications

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“…B7-1 is a transmembrane protein normally expressed on antigen presenting cells capable of providing either a co-stimulatory or co-inhibitory signal depending upon whether it interacts with its counter-receptor CD28 or CTLA4, respectively [61, 62]. The expression has been reported to portend a poor prognosis for patients with pancreatic cancer [63] and the combination of B7-1 and B7-H1 has been suggested as a diagnostic factor [18]. As such, determining the manner(s) by which B7-1 is regulated and its role in pancreatic cancer progression is critical to developing effective immunotherapeutic approaches for this deadly disease as recently shown for other solid tumors such as lung, melanoma, head and renal cancers [64–67].…”

Section: Discussionmentioning

confidence: 99%

B7-1 drives TGF-β stimulated pancreatic carcinoma cell migration and expression of EMT target genes

Kang¹,

Jung²,

Leof³

2019

PLoS ONE

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B7-1 proteins are routinely expressed on the surface of antigen presenting cells (APC) and within the innate immune system. They function to establish a biologically optimal and dynamic balance between immune activation and inhibition or self-tolerance. Interactions between B7-1 and its receptors, which include CD28, CTLA4 and PD-L1, contribute to both stimulatory as well as inhibitory or homeostatic regulation. In the current study, we investigated whether the tumor-promoting actions of transforming growth factor beta (TGF-β) disrupted this equilibrium in pancreatic cancer to promote malignant progression and an enhanced means to evade immune detection. The data show that B7-1 is (i) upregulated following treatment of pancreatic carcinoma cells with TGF-β; (ii) induced by TGF-β via both Smad2/3-dependent and independent pathways; (iii) required for pancreatic tumor cell in vitro migration/invasion; and (iv) necessary for TGF-β regulated epithelial-mesenchymal transition (EMT) through induction of Snail family members. Results from the proposed studies provide valuable insights into mechanisms whereby TGF-β regulates both the innate immune response and intrinsic properties of pancreatic tumor growth.

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Section: Discussionmentioning

confidence: 99%

B7-1 drives TGF-β stimulated pancreatic carcinoma cell migration and expression of EMT target genes

Kang¹,

Jung²,

Leof³

2019

PLoS ONE

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“…The authors, however, did not find any correlation with patient survival. Previous studies have assessed individual serum cytokines in relation to the survival of patients with cancer [ 26 , 27 ], although the effect of cytokine networks remained underexplored. Cytokine networks, rather than individual cytokines, provide a ‘high-resolution’ insight into disease mechanisms involved in pathogenesis and progression i.e.…”

Section: Discussionmentioning

confidence: 99%

Cytokine Networks and Survivin Peptide-Specific Cellular Immune Responses Predict Improved Survival in Patients With Glioblastoma Multiforme

et al. 2018

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PurposeWe investigated serum cytokine and T-cell responses directed against tumour-associated antigens (TAAs) in association with survival of patients with glioblastoma multiforme (GBM).Patients and MethodsPeripheral blood from 205 treatment-naïve patients with glioma (GBM = 145; non-GBM = 60) was obtained on the day of surgery to measure (i) circulating T-cells reacting to viral antigens and TAAs, in the presence or absence of cytokine conditioning with IL-2/IL-15/IL-21 or IL-2/IL-7, and (ii) serum cytokine levels (IL-4, IL-5, IL-6, TNF-α, IFN-γ and IL-17A). Patients were followed-up for at least 1000 days post-surgery. Survivin protein and gene expression in resected GBM tumour tissue were confirmed by immunohistochemistry and real-time polymerase chain reaction, respectively. Antigen-specific T-cell responses were gauged by ICS (intracellular cytokine production). Associations between patient survival and immunological reactivity patterns were analysed using univariate and multivariate statistics.ResultsApproximately 2% of patients with GBM and 18% of patients with non-GBM glioma, were alive beyond 1000 days of surgery. Univariate analysis indicated that the combination of three cytokines (IL-4/IL-5/IL-6, p = .0022; IFN-γ/TNF-α/IL-17A, p = .0083) but not a ‘partial’ combination of these cytokines, the IFN-γ immune response to EBV-EBNA-1 (p < .0001) as well as T-cell responses to the survivin97–111 peptide (p = .0152) correlated with longer survival among patients with GBM. Multivariate analysis identified survivin97–111-directed IFN-γ production with IL-2/IL-15/IL-21 conditioning (p = .024), and the combined presence of serum IFN-γ/TNF-α/IL-17a (p = .003) as independent predictors of survival.ConclusionSerum cytokine patterns and lymphocyte reactivity to survivin97–111, particularly with IL-2, IL-15 and IL-21 conditioning may be instrumental in predicting survival among patients with GBM. This has implications for clinical follow-up of patients with GBM and the targeted development of immunotherapy for patients with CNS tumours.

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“…This is the first time that B7.1 has been linked to IPMN. In a previous study, the protein marker B7-1 was included in a serum biomarker panel for pancreatic cancer outcome prediction [23]. Overexpression of B7-1 and B7-H1 has also been observed in pancreatic cancer tissues compared to normal pancreas [24].…”

Section: Discussionmentioning

confidence: 99%

High-density and targeted glycoproteomic profiling of serum proteins in pancreatic cancer and intraductal papillary mucinous neoplasm

Aronsson

Andersson

Bauden

et al. 2018

Scandinavian Journal of Gastroenterology

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Objective: Glycoproteomics is an emerging subfield of proteomics. Tumor-specific variations in protein glycosylation might be potential targets for the development of new cancer diagnostics. Here, we performed high-throughput screening and targeted verification of glycome alterations in serum samples from patients with pancreatic cancer and the precancerous lesion intraductal papillary mucinous neoplasm (IPMN). Material and methods: The glycosylation profile of 1000 proteins was mapped in a discovery cohort comprising serum samples from 16 individuals, including 8 patients with pancreatic cancer and 8 healthy controls. The top 10 glycoprotein biomarker candidates with the highest signal intensity difference in glycosylation levels were evaluated in a cohort consisting of 109 serum samples, including 49 patients with resectable pancreatic cancer, 13 patients with resectable noninvasive IPMN and 47 healthy controls, using a targeted assay. Results: Multivariable analysis defined sets of panels comprising CA19-9 and distinctively glycosylated proteins for discrimination between pancreatic cancer, IPMN and healthy controls. A panel including CA 19-9, IL.17E, B7.1 and DR6 gave an AUC of 0.988 at 100% sensitivity at 90% specificity for the discrimination of stage 1 pancreatic cancer and healthy controls. B7.1 was found to be a valuable biomarker for differentiating between IPMN and healthy controls, with better performance alone than CA 19-9. Conclusions: Measurement of protein glycosylation profiles in serum may aid in the early detection of pancreatic cancer and precursor lesions.

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Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

Cited by 20 publications

References 61 publications

B7-1 drives TGF-β stimulated pancreatic carcinoma cell migration and expression of EMT target genes

B7-1 drives TGF-β stimulated pancreatic carcinoma cell migration and expression of EMT target genes

Cytokine Networks and Survivin Peptide-Specific Cellular Immune Responses Predict Improved Survival in Patients With Glioblastoma Multiforme

High-density and targeted glycoproteomic profiling of serum proteins in pancreatic cancer and intraductal papillary mucinous neoplasm

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