Cytokine production by blood immune cells, tumor and its microenvironment, characteristic of extracellular matrix in patients with invasive ductal carcinoma of no special type

Autenshlyus, A. I.; Davletova, K I; Studenikina, A. A.; Mikhaylova, E. S.; Вараксин, Н. А.; Zhurakovsky, I. P.; Проскура, А В; Sidorov, S. V.; Lyakhovich, V. V.

doi:10.18097/pbmc20196505424

Cited by 4 publications

(5 citation statements)

References 24 publications

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“…It is known that (i) VEGF is a key mediator of angiogenesis in both nominally healthy people and patients with malignant tumors 17 ; (ii) IL-18 creates an immunosuppressive environment for the tumor 18 ; and (iii) TNF-α, GM-CSF, and MCP-1 induce the synthesis of matrix metalloproteinases and activation of epithelial–mesenchymal transition. 11 Therefore, their low spontaneous secretion by the luminal A subtype may be one of the reasons for the relatively slow malignant progression typical for this molecular subtype. 3 , 4 The cultured tumors of the triple-negative molecular subtype featured the highest spontaneous secretion of IL-1β in our study.…”

Section: Resultsmentioning

confidence: 99%

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Cytokines in various molecular subtypes of breast cancer

Autenshlyus

Davletova

Вараксин

et al. 2021

Int J Immunopathol Pharmacol

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Introduction Breast cancer is a heterogeneous disease that has multiple molecular and morphological subtypes. Nonetheless, the relation between various molecular subtypes and functional characteristics of a tumor in terms of cytokine secretion remains unknown. Methods We studied spontaneous and mitogen-induced cytokine secretion by invasive breast carcinoma of no special type (IBC NST; cultured tumors and cultured peripheral blood cells), depending on a molecular tumor subtype (where “mitogens” means “polyclonal activators” (PA): phytohemagglutinin p, phytohemagglutinin M, concanavalin A, and Escherichia coli lipopolysaccharide). Enzyme-linked immunosorbent assays were used to determine concentrations of IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, and MCP-1 in culture supernatants of the tumors and peripheral blood cells. Results The luminal B HER2-positive molecular subtype of IBC NST was found to feature the highest spontaneous secretion of IL-6 and IL-8 and the highest mitogen-induced secretion of IL-6, IL-8, IL-1Ra, and TNF-α by tumors; the highest mitogen-induced secretion of IL-2, IL-6, IL-8, IL-1β, TNF-α, IFN-γ, and G-CSF by peripheral blood cells; and the highest cytokine-producing potential (the ratio of mitogen-induced to spontaneous secretion) of peripheral blood cells for the secretion of IL-6, IL-8, and IL-1Ra as compared to other molecular subtypes. The triple-negative subtype of IBC NST was characterized by the lowest cytokine-producing potential of tumors for the secretion of IL-6 and IL-8 as compared to other molecular subtypes as well as a lower “stimulation index of polyclonal activators” (calculated as (cytokine secretion after incubation with PA)/(spontaneous cytokine secretion)) for IL-18 secretion as compared to luminal subtypes. The XYZ correlated with a suppressive effect of PA on cytokine secretion by tumors of the triple-negative molecular subtype. Conclusion Therefore, our findings indicate that in IBC NST of luminal B HER2-positive and triple-negative molecular subtypes, the cytokine network has distinctive functional features.

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Section: Resultsmentioning

confidence: 99%

“…2 with PA: 2 μg/mL phytohemagglutinin P, 2 μg/mL phytohemagglutinin M, 4 μg/mL concanavalin A, and 2 μg/mL lipopolysaccharide from E. coli . 11 Vial no. 1 and no.…”

Section: Methodsmentioning

confidence: 99%

Cytokines in various molecular subtypes of breast cancer

Autenshlyus

Davletova

Вараксин

et al. 2021

Int J Immunopathol Pharmacol

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“…35,36 It has been reported that lymphocytes can regulate the ECM and endothelial cell function to improve tumor vasculature. 37,38 After sequential fat grafting, the TNFα signaling via NFκB was the most significant down-modulated gene set. We found 3 genes (PAI-1, EDN1, and NFKBIA) from this gene set recognized as hub genes were reduced after sequential fat grafting (eFigure 9B-D in Supplement 1).…”

Section: Discussionmentioning

confidence: 99%

“…T lymphocyte infiltration is a common histologic feature of morphea and is believed to be associated with disease progression . It has been reported that lymphocytes can regulate the ECM and endothelial cell function to improve tumor vasculature . After sequential fat grafting, the TNFα signaling via NFκB was the most significant down-modulated gene set.…”

Section: Discussionmentioning

confidence: 99%

Clinical, Histologic, and Transcriptomic Evaluation of Sequential Fat Grafting for Morphea

Liu,

Wang,

Zhang

et al. 2024

JAMA Dermatol

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ImportanceMorphea is a rare disease of unknown etiology without satisfactory treatment for skin sclerosis and soft tissue atrophy.ObjectiveTo provide clinical, histologic, and transcriptome evidence of the antisclerotic and regenerative effects of sequential fat grafting with fresh fat and cryopreserved stromal vascular fraction gel (SVF gel) for morphea.Design, Setting, and ParticipantsThis single-center, nonrandomized controlled trial was conducted between January 2022 and March 2023 in the Department of Plastic and Reconstructive Surgery of Nanfang Hospital, Southern Medical University and included adult participants with early-onset or late-onset morphea who presented with varying degrees of skin sclerosis and soft tissue defect.InterventionsGroup 1 received sequential grafting of fresh fat and cryopreserved SVF gel (at 1 and 2 months postoperation). Group 2 received single autologous fat grafting. All patients were included in a 12-month follow-up.Main Outcome and MeasuresThe primary outcome included changes in the modified Localized Scleroderma Skin Severity Index (mLoSSI) and Localized Scleroderma Skin Damage Index (LoSDI) scores as evaluated by 2 independent blinded dermatologists. The histologic and transcriptome changes of morphea skin lesions were also evaluated.ResultsOf 44 patients (median [IQR] age, 26 [23-33] years; 36 women [81.8%]) enrolled, 24 (54.5%) were assigned to group 1 and 20 (45.5%) to group 2. No serious adverse events were noted. The mean (SD) mLoSSI scores at 12 months showed a 1.6 (1.50) decrease in group 1 and 0.9 (1.46) in group 2 (P = .13), whereas the mean (SD) LoSDI scores at 12 months showed a 4.3 (1.34) decrease in group 1 and 2.1 (1.07) in group 2 (P &lt; .001), indicating that group 1 had more significant improvement in morphea skin damage but not disease activity compared with group 2. Histologic analysis showed improved skin regeneration and reduced skin sclerosis in group 1, whereas skin biopsy specimens of group 2 patients did not show significant change. Transcriptome analysis of skin biopsy specimens from group 1 patients suggested that tumor necrosis factor α signaling via NFκB might contribute to the immunosuppressive and antifibrotic effect of sequential fat grafting. A total of 15 hub genes were captured, among which many associated with morphea pathogenesis were downregulated and validated by immunohistochemistry, such as EDN1, PAI-1, and CTGF.Conclusions and RelevanceThe results of this nonrandomized trial suggest that sequential fat grafting with fresh fat and cryopreserved SVF gel was safe and its therapeutic effect was superior to that of single autologous fat grafting with improved mLoSSI and LoSDI scores. Histological and transcriptomic changes further support the effectiveness after treatment.Trial RegistrationChinese Clinical Trial Registry identifier: ChiCTR2200058003

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“…The TME components were shown to influence the malignant behaviour of PC [ 8 , 9 , 10 ]. One major impact are cytokines released by both tumour cells directly and by TME components such as cancer-associated fibroblasts (CAFs) and tumour-associated macrophages (TAMs) [ 11 , 12 , 13 ], as they contribute to aggressive cancer progression, metastasis, and suppression of tumour-directed immune surveillance mechanisms [ 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Loss of Interleukin-13-Receptor-Alpha-1 Induces Apoptosis and Promotes EMT in Pancreatic Cancer

Shi

Shen

Kang

et al. 2022

IJMS

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In search of new therapies for pancreatic cancer, cytokine pathways have attracted increasing interest in recent years. Cytokines play a vital role in the crosstalk between tumour cells and the tumour microenvironment. The related inflammatory cytokines IL-4 and IL-13 can regularly be detected at increased levels in the microenvironment of pancreatic cancer. They share a receptor heterodimer consisting of IL-4Rα and IL-13Rα1. While IL-4Rα induces a more oncogenic phenotype, the role of IL-13Rα1 was yet to be determined. ShRNA-based knockdown of IL-13Rα1 was performed in Capan-1 and MIA PaCa-2. We assessed cell growth and migratory capacities under the influence of IL-13Rα1. Pathway alterations were detected by immunoblot analysis. We now have demonstrated that the loss of IL-13Rα1 induces apoptosis in pancreatic cancer cells. This was associated with an epithelial-to-mesenchymal transition. Loss of IL-13Rα1 also abolished the effects of exogenous IL-4 and IL-13 stimulation. Interestingly, in wild type cells, cytokine stimulation caused a similar increase in migratory capacities as after IL-13Rα1 knockdown. Overall, our results indicate the vital role of IL-13Rα1 in the progression of pancreatic cancer. The differential expression of IL-4Rα and IL-13Rα1 has to be taken into account when considering a cytokine-targeted therapy in pancreatic cancer.

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Cytokine production by blood immune cells, tumor and its microenvironment, characteristic of extracellular matrix in patients with invasive ductal carcinoma of no special type

Cited by 4 publications

References 24 publications

Cytokines in various molecular subtypes of breast cancer

Cytokines in various molecular subtypes of breast cancer

Clinical, Histologic, and Transcriptomic Evaluation of Sequential Fat Grafting for Morphea

Loss of Interleukin-13-Receptor-Alpha-1 Induces Apoptosis and Promotes EMT in Pancreatic Cancer

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