Gene Summary

Gene:IL10; interleukin 10
Aliases: CSIF, TGIF, GVHDS, IL-10, IL10A
Summary:The protein encoded by this gene is a cytokine produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1 cytokines, MHC class II Ags, and costimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. This cytokine can block NF-kappa B activity, and is involved in the regulation of the JAK-STAT signaling pathway. Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract. Mutations in this gene are associated with an increased susceptibility to HIV-1 infection and rheumatoid arthritis.[provided by RefSeq, May 2011]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Source:NCBIAccessed: 01 September, 2019


What does this gene/protein do?
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Pathways:What pathways are this gene/protein implicaed in?
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Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 01 September 2019 using data from PubMed using criteria.

Literature Analysis

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Tag cloud generated 01 September, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (7)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: IL10 (cancer-related)

Hassan EA, Ahmed EH, Nafee AM, et al.
Regulatory T Cells, IL10 and IL6 in HCV Related Hepatocellular Carcinoma after Transarterial Chemoembolization (TACE).
Egypt J Immunol. 2019; 26(1):69-78 [PubMed] Related Publications
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. Tumors can recruit and promote the expansion of regulatory T cells (Tregs) to suppress antitumor immune responses for survival and progression. Furthermore, there is a strong evidence for the potential roles of cytokines in promoting HCC carcinogenesis and progression. We aimed to evaluate the frequency of Treg cells and serum levels of IL6 and IL10 before and after transarterial chemoembolization (TACE). We carried out a cross-sectional study at Assiut University hospitals that included 34 HCC patients and 10 matched apparently healthy controls. Peripheral Treg frequency was evaluated by Flow cytometry. IL6 and IL10 serum levels were evaluated by ELISA before and after TACE. HCC patients had a significantly higher level of IL6 and IL10 when compared to the control group (P=0.0002, P < 0.0001), respectively. However, after treatment, there was an elevation in the levels of IL6 and IL10 followed by a decrease to the baseline levels. Patients with large tumors (≥5 cm) showed higher levels of both IL 6 and IL 10 than those with smaller tumors. Moreover, HCC patients showed a higher frequency of Treg cells in comparison to the controls (P=0.002). No significant correlation was observed between the frequency of Treg cells and IL10 before and after treatment (r=0.38, P=0.30). In conclusion, HCC patients have significantly higher levels of IL 6, IL 10 and a higher percentage of Tregs than control individuals. Treg levels are altered after chemoembolization. IL 6 have a potential in reflecting the patient's condition after treatment, thus, can help in monitoring therapy.

Osiagwu DD, Azenabor AE, Osijirin AA, et al.
Evaluation of interleukin 8 and interleukin 10 cytokines in liquid based cervical cytology samples.
Pan Afr Med J. 2019; 32:148 [PubMed] Free Access to Full Article Related Publications
Introduction: inflammatory cytokines have been associated with various cancers, including cervical cancers. Interpreting cytokine expression in liquid based cervical samples is quite challenging. This study is aimed at evaluating the levels of interleukin 8 and 10 in liquid based cervical samples.
Methods: this is a descriptive analytical study carried out on eighty five (85) subjects aged between 23 and 68 years. Cervical samples were collected in liquid based medium and smears later examined after staining with Papanicolaou technique. These were categorized into low grade intra-epithelial lesion/malignancy, high grade intraepithelial lesion/malignancy according to the degree of dyskaryosis. Concentrations of interleukin 8 and interleukin 10 in the samples were determined by enzyme linked immunosorbent assay.
Results: the mean age, standard deviation (SD) of the study subjects were 40.6 (7.8) years. A total number of 79 females (92.9%) were negative for intra-epithelial lesion/malignancy (NILM), while 4 (4.71%) and 2 (2.35%) were positive for low grade intra-epithelial lesion/malignancy (LILM) and high grade intra-epithelial lesion (HILM) respectively. While mean levels of interleukin 8 increased with the degree of malignancy, (107.27 ± 11.88pg/ml) in LILM, (114.80 ± 2.12pg/ml) in HILM when compared with NILM (88.39 ± 18.06pg/ml), (f = 0.700, p = 0.018); the mean levels of interleukin 10 was comparable between these groups (p ≥ 0.05). Pearson correlation coefficient analysis showed a negative association between interleukin 8 and interleukin 10 (r = -1.999, p = 0.000) in LILM.
Conclusion: interleukin 8 cytokines in cervical cancer is associated with the degree of malignancy. Possible anti-inflammatory effect of interleukin 10 was not observed.

Damo M, Joshi NS
Nat Immunol. 2019; 20(6):674-675 [PubMed] Related Publications

Germini DE, Franco MIF, Fonseca FLA, et al.
Association of expression of inflammatory response genes and DNA repair genes in colorectal carcinoma.
Tumour Biol. 2019; 42(4):1010428319843042 [PubMed] Related Publications
Inflammation is an important etiological factor of colorectal carcinoma and may be related to colorectal carcinoma growth and proliferation. This study aimed to verify whether the presence of chronic inflammation represented by tumor necrosis factor-α, interleukin-2, interleukin-6, and interleukin-10 gene expression is related to hMLH1, hMSH2, hMSH6, and PMS2 gene expression and the corresponding protein levels of these genes from the DNA repair system. A total of 83 patients were operated on for curative or palliative colorectal carcinoma. Expression of the inflammatory response genes tumor necrosis factor-α, interleukin-2, interleukin-6, and interleukin-10 as well as expression of the hMLH1, hMSH2, hMSH6, and PMS2 genes of the DNA repair system (mismatch repair) and the expression levels of the corresponding mismatch repair proteins were measured in neoplastic tissue by reverse transcription polymerase chain reaction and immunohistochemistry, respectively. Associations were observed between hMSH6 mRNA expression and interleukin-2 mRNA expression (p = 0.026) as well as between hMLH1 and hMSH2 gene expression and tumor necrosis factor-α gene expression (p = 0.042). Higher tissue levels of interleukin-2 and tumor necrosis factor-α gene expression were associated with lower hMSH6, hMLH1, and hMSH2 gene expression.

Niedźwiecki M, Budziło O, Adamkiewicz-Drożyńska E, et al.
J Immunol Res. 2019; 2019:2816498 [PubMed] Free Access to Full Article Related Publications
Regulatory T-cells (Tregs) are a very important subtype of lymphocytes when it comes to self-control in the human immunological system. Tregs are decisive not only in the protection against destruction of own tissues by autoimmune immunocompetent cells but also in the immunological answer to developing cancers. On the other hand, Tregs could be responsible for the progression of acute and chronic leukemias. In our study, we review publications available in the PUMED database concerning acute leukemia, with a particular emphasis on child's leukemias. The percentage of regulatory T-lymphocytes in peripheral blood and bone marrow was elevated compared to those in healthy individuals and correlated with progressive disease. Regulatory T-cells taken from children diagnosed with leukemia showed a higher suppressive capability, which was confirmed by detecting elevated levels of secreted IL-10 and TGF-beta. The possibility of pharmacological intervention in the self-control of the immunological system is now under extensive investigation in many human cancers. Presumably, Treg cells could be a vital part of targeted therapies. Routine Treg determination could be used to assess the severity of disease and prognosis in children with acute lymphoblastic leukemia. This proposition results from the fact that in some studies, higher percentage of Treg cells in peripheral blood was demonstrated. However, observations confirming these facts are scarce; thus, extrapolating them to the population of children with hematological malignancies needs to be verified in additional studies.

Sawant DV, Yano H, Chikina M, et al.
Adaptive plasticity of IL-10
Nat Immunol. 2019; 20(6):724-735 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Regulatory T cells (T

Barilla RM, Diskin B, Caso RC, et al.
Specialized dendritic cells induce tumor-promoting IL-10
Nat Commun. 2019; 10(1):1424 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
The drivers and the specification of CD4

Goud EVSS, Malleedi S, Ramanathan A, et al.
Association of Interleukin-10 Genotypes and Oral Cancer Susceptibility in Selected Malaysian Population: A Case- Control Study
Asian Pac J Cancer Prev. 2019; 20(3):935-941 [PubMed] Related Publications
Background: Interleukin-10 (IL10) genotypes have been closely correlated to the susceptibility for oral squamous cell carcinoma. More than half of oral cancers in the world occur in Asia with estimated 168,850 new cases were diagnosed in this geographical region alone. Considering the rising numbers of oral cancer cases in Malaysia, association of IL10 A1082G gene polymorphism was correlated. Methodology: 41 oral squamous cell carcinoma (OSCC) cases and 48 healthy controls of comparable age, gender, and with habits like smoking, alcohol consumption and betel quid chewing were selected. In this case-control study, samples were collected from the Oral Cancer Research and Coordinating Centre (OCRCC), Faculty of Dentistry, University of Malaya, Malaysia. Genotyping conditions were evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The PCR products were subjected to digestion by MnlI enzyme (NEB, UK) to screen for the IL10 A-1082G. Digested DNA products were analyzed by electrophoresis on 4% (w/v) agarose gel, stained with ethidium bromide and imaged under UV illumination. Chi-square test and Fisher’s Exact test were used in statistical analysis. Results: AG genotypes were present in 81.3% and 86.0% of healthy control and OSCC cases respectively (OR=0.468, 95% CI=0.133-1.653). No significant association was found between IL10 A1082G polymorphism with risk habits, clinico-pathological parameters and 5-years overall survival. The findings also show no significant correlation between the IL10 genotype and features of OSCC within the case group as measured by tumor size, lymph node involvement, stage, invasive front, grading, depth, pattern of invasion. Conclusion: This study suggests that functional polymorphism AG of IL10 A1082G may have no influence with OSCC susceptibility. However, further investigation with larger sample sizes can be conducted to provide additional evidence to support the lack of association of IL10 A1082G polymorphism in oral cancer.

Wang X, Wang G, Wang Z, et al.
PD-1-expressing B cells suppress CD4
Mol Immunol. 2019; 109:20-26 [PubMed] Related Publications
B cell-mediated regulatory function is instrumental to the maintenance of tolerance, but may also contribute to immune dysfunction during infectious diseases and malignancies. In this study, we investigated a subset of B cells characterized by PD-1 expression. Data showed that these PD-1

Schiavon V, Duchez S, Branchtein M, et al.
Microenvironment tailors nTreg structure and function.
Proc Natl Acad Sci U S A. 2019; 116(13):6298-6307 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Natural regulatory T cells (nTregs) ensure the control of self-tolerance and are currently used in clinical trials to alleviate autoimmune diseases and graft-versus-host disease after hematopoietic stem cell transfer. Based on CD39/CD26 markers, blood nTreg analysis revealed the presence of five different cell subsets, each representing a distinct stage of maturation. Ex vivo added microenvironmental factors, including IL-2, TGFβ, and PGE2, direct the conversion from naive precursor to immature memory and finally from immature to mature memory cells, the latest being a no-return stage. Phenotypic and genetic characteristics of the subsets illustrate the structural parental maturation between subsets, which further correlates with the expression of regulatory factors. Regarding nTreg functional plasticity, both maturation stage and microenvironmental cytokines condition nTreg activities, which include blockade of autoreactive immune cells by cell-cell contact, Th17 and IL-10 Tr1-like activities, or activation of TCR-stimulating dendritic cell tolerization. Importantly, blood nTreg CD39/CD26 profile remained constant over a 2-y period in healthy persons but varied from person to person. Preliminary data on patients with autoimmune diseases or acute myelogenous leukemia illustrate the potential use of the nTreg CD39/CD26 profile as a blood biomarker to monitor chronic inflammatory diseases. Finally, we confirmed that naive conventional CD4 T cells, TCR-stimulated under a tolerogenic conditioned medium, could be ex vivo reprogrammed to FOXP3 lineage Tregs, and further found that these cells were exclusively committed to suppressive function under all microenvironmental contexts.

Silva JR, Sales NS, Silva MO, et al.
Expression of a soluble IL-10 receptor enhances the therapeutic effects of a papillomavirus-associated antitumor vaccine in a murine model.
Cancer Immunol Immunother. 2019; 68(5):753-763 [PubMed] Related Publications
The presence of IL-10, produced either by tumor cells or immunosuppressive cells, is frequently associated with a poor prognosis for cancer progression. It may also negatively impact anticancer treatments, such as immunotherapies, that otherwise would promote the activation of cytotoxic T cells capable of detecting and destroying malignant cells. In the present study, we evaluated a new adjuvant approach for anticancer immunotherapy using a plasmid vector encoding a soluble form of the IL-10 receptor (pIL-10R). pIL-10R was coadministered to mice with a DNA vaccine encoding the type 16 human papillomavirus (HPV-16) E7 oncoprotein genetically fused with glycoprotein D of herpes simplex virus (HSV) (pgDE7h). Immunization regimens based on the coadministration of pIL-10R and pgDE7h enhanced the antitumor immunity elicited in mice injected with TC-1 cells, which express HPV-16 oncoproteins. The administration of the DNA vaccines by in vivo electroporation further enhanced the anticancer effects of the vaccines, leading to the activation of tumor-infiltrating polyfunctional E7-specific cytotoxic CD8

Rothemich A, Arthur JC
The Azoxymethane/Il10
Methods Mol Biol. 2019; 1960:215-225 [PubMed] Related Publications
Mouse models have proved essential for generating a mechanistic understanding of human disease processes. The azoxymethane/interleukin-10 knockout (AOM/Il10

Shokrzadeh M, Mohammadpour A, Hoseini V, et al.
Arq Gastroenterol. 2018 Oct-Dec; 55(4):385-389 [PubMed] Related Publications
BACKGROUND: Gastric adenocarcinoma is the fourth most common cause of cancer-associated death worldwide.
OBJECTIVE: We evaluated the immunological status of patients with gastric cancer before surgery and circulating cytokines as potential diagnostic biomarkers for gastric cancer.
METHODS: We included 90 healthy controls and 95 patients with distal Gastric adenocarcinoma in Mazandaran, Sari, Iran. We measured serum IL-2, IL-10 and IL-12 Levels by a sandwich enzyme-linked immunosorbent assay using the IBL international GMBH kit.
RESULTS: The serum IL-10 levels in the patients with Gastric adenocarcinoma were significantly higher than those of the healthy controls (P=0.02). There were no significant differences in serum IL-2 and IL-12 levels between patients with gastric cancer and healthy controls.
CONCLUSION: Increased levels of IL-10 might be useful as diagnostic biomarkers for Gastric adenocarcinoma; however, this needs to be confirmed with larger number of patients and with control groups other than blood donors, properly age paired. These results suggest that positive expression of IL-10 may be useful as a molecular marker to distinguish stage of gastric cancers which can be more readily controlled.

Maknı L, Ben Hamda C, Al-ansarı A, et al.
Association of common IL-10 promoter gene variants with the susceptibility to head and neck cancer in Tunisia
Turk J Med Sci. 2019; 49(1):123-128 [PubMed] Related Publications
Background/aim: We investigated the association of three IL-10 promoter single-nucleotide polymorphisms and altered IL-10 plasma levels with the risk of head and neck cancer (HNC).
Materials and methods: Study subjects comprised 194 HNC patients [137 nasopharyngeal cancer (NPC) and 57 laryngeal cancer (LC)], and 263 healthy controls. Genotyping of rs1800896 (-1082A>G), rs1800871 (-819C>T), and rs1800872 (-592A>C) IL-10 variants was performed by real-time PCR; IL-10 levels were measured by enzyme amplified immuno sensitivity assay (EAISA).
Results: Study subjects comprised 194 HNC patients [137 nasopharyngeal cancer (NPC) and 57 laryngeal cancer (LC)], and 263 healthy controls. Genotyping of rs1800896 (-1082A>G), rs1800871 (-819C>T), and rs1800872 (-592A>C) IL-10 variants was performed by real-time PCR; IL-10 levels were measured by enzyme amplified immuno sensitivity assay (EAISA).
Conclusion: Our results demonstrate that IL-10-1082, IL-10-819, and IL-10-592 variants, and haplotypes GC and GT constitute biomarkers for early detection of HNC, especially NPC subtype. IL-10 -819T/C and TA haplotype may be used as biomarkers for early detection of LC.

Raucci MG, Fasolino I, Caporali M, et al.
Exfoliated Black Phosphorus Promotes in Vitro Bone Regeneration and Suppresses Osteosarcoma Progression through Cancer-Related Inflammation Inhibition.
ACS Appl Mater Interfaces. 2019; 11(9):9333-9342 [PubMed] Related Publications
Nowadays chemotherapy is the main treatment for osteosarcoma disease, even if limited by the lack of selectivity between healthy and cancer cells during the inhibition of cell division. Herein, we propose the use of few-layer two-dimensional black phosphorous (2D bP) as an alternative tool for osteosarcoma treatment and report how 2D bP can stimulate newly forming bone tissue generation after osteosarcoma resection. In our study, we have developed an in vitro model to evaluate the efficacy of 2D bP material with and without near-infrared light irradiation treatment, and we have demonstrated that the presence of 2D bP without treatment inhibits the metabolic activity of osteosarcoma cells (SAOS-2) while inducing both the proliferation and the osteogenic differentiation of human preosteoblast cells (HOb) and mesenchymal stem cells. Furthermore, we also propose an in vitro coculture model (SAOS-2 and HOb cell lines) in order to study the effect of 2D bP on inflammatory response related to cancer. On this coculture model, 2D bP may increase anti-inflammatory cytokine generation (i.e., interleukin-10) and inhibit proinflammatory mediators synthesis (i.e., interleukin-6), thus suggesting the opportunity to prevent cancer-related inflammation. Finally, we have demonstrated that 2D bP represents a promising candidate for future regenerative medicine and anticancer applications.

Wei Y, Lao XM, Xiao X, et al.
Plasma Cell Polarization to the Immunoglobulin G Phenotype in Hepatocellular Carcinomas Involves Epigenetic Alterations and Promotes Hepatoma Progression in Mice.
Gastroenterology. 2019; 156(6):1890-1904.e16 [PubMed] Related Publications
BACKGROUND & AIMS: Little is known about the composition and generation of plasma cell subsets in patients with hepatocellular carcinoma (HCC) and how these associate with outcomes. We investigated whether, or how, plasma cells differentiate and function in patients with HCC and mice with liver tumors.
METHODS: We analyzed subset composition and distribution of plasma cells in HCC samples from 342 patients who underwent curative resection at the Cancer Center of Sun Yat-sen University in China; samples of non-tumor liver tissue were used as controls. We associated plasma cell profiles with patient outcomes. Tissue-derived leukocytes were analyzed by flow cytometry and real-time polymerase chain reaction. The ability of macrophages to regulate plasma cell differentiation was determined in ex vivo cultures of cells from human HCC tissues. C57BL/6 and BALB/c mice were given injections of Hepa1-6 cells, which formed hepatomas, or H22 cells, which formed ascitic hepatomas. Gene expression patterns were analyzed in human HCC, mouse hepatoma, and non-tumor tissues by real-time polymerase chain reaction. Mice with hepatomas were given injections of GSK126 (an inhibitor of histone H3 lysine 27 methyltransferase [EZH2]) and 5-AZA-dC (an inhibitor of DNA methyltransferases); tumor tissues were analyzed by immunofluorescence and immunohistochemistry for the presence of immune cells and cytokines.
RESULTS: B cells isolated from HCCs had somatic hypermutations and class-switch recombinations to the IgG phenotype that were not observed in non-tumor tissues. Increased level of plasma cells correlated with poor outcomes of patients. Activated CD4
CONCLUSIONS: Human HCC tissues contain B cells with class-switch recombinations to the IgG phenotype. Activated CD4

Abedinzadeh M, Neamatzadeh H, Jafari M, et al.
Association of Interleukin-10 -1082A>G (rs1800896) Polymorphism with Predisposition to Breast Cancer: a Meta-Analysis based on 17 Case-Control Studies.
Rev Assoc Med Bras (1992). 2018; 64(8):756-764 [PubMed] Related Publications
INTRODUCTION: The association between the between IL-10 -1082A>G (rs1800896) polymorphism and breast cancer has been evaluated by several number case-control studies. However, these studies might be underpowered to reveal the true association.
OBJECTIVE: We have performed a comprehensive meta-analysis to investigate the association IL-10 -1082A>G polymorphism and breast cancer.
MATERIALS AND METHODS: A systematic literature search was conducted using PubMed, Google Scholar, and Web of Science up to September 20, 2017. Data was analysed with CMA software to identify the strength of the association by pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs).
RESULTS: A total of 17 case-control studies involving 3275 cases and 3416 controls obtained from database searches were examined. Overall, there was no significant association between IL-10 -1082A>G polymorphism and breast cancer risk under all genetic models. No significant publication bias was found for the five genetic models (G vs.
A: OR = 1.184, 95% CI = 0.895-1.180, p= 0.230; GG vs. AA: OR = 1.430, 95% CI = 0.927-2.204, p= 0.106; GA vs. AA: OR = 0.966, 95% CI = 0.765-1.221, p= 0.774; GG+GA vs. AA: OR = 0.957, 95% CI = 0.697-1.314, p= 0.786; and GG vs. GA+AA: OR = 1.221, 95% CI = 0.981-1.518, p= 0.073). Moreover, there was no significant association between the IL-10 -1082A>G polymorphism and breast cancer risk by ethnicity.
CONCLUSION: Our findings indicated that IL-10 -1082A>G (rs1800896) polymorphism might not be a risk factor for the development of breast cancer.

Wang Y, Cheng J, Yang L, et al.
Ropivacaine for Intercostal Nerve Block Improves Early Postoperative Cognitive Dysfunction in Patients Following Thoracotomy for Esophageal Cancer.
Med Sci Monit. 2019; 25:460-465 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
BACKGROUND Ropivacaine is commonly used as an intercostal nerve block, but its effects on postoperative cognitive dysfunction (POCD) have not previously been investigated. This study aimed to examine the effects of the use of ropivacaine as an intercostal nerve block on early POCD, postoperative analgesia, and inflammation in patients following thoracotomy for esophageal cancer. MATERIAL AND METHODS One hundred patients with esophageal cancer undergoing thoracotomy were randomly divided into a group with intercostal nerve block (group A) (n=50) and a control group (group B) (n=50). The cognitive function score and visual analog scale (VAS) scores for pain were measured at one hour before surgery (T1), two hours after surgery (T2), 12 hours after surgery (T3), and 24 hours after surgery (T4). Blood samples were collected at each time point, and plasma levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-10, and S100-β were measured using an enzyme-linked immunosorbent assay (ELISA). Cognitive function was determined using the Mini-Mental State Examination (MMSE) scale. RESULTS The VAS scores in group A were significantly lower compared with group B (p<0.05). In the T2, T3, and T4 time points, group A had significantly increased MMSE scores compared with group B (p<0.05). Compared with group B, the levels of IL-6 and TNF-a were significantly decreased in group A at T3 and T4 (p<0.05), while the levels of IL-10 were significantly increased (p<0.05) when compared with group A. CONCLUSIONS The use of the intercostal nerve block, ropivacaine, improved early PCOD in patients following thoracotomy for esophageal cancer.

Das S, Bar-Sagi D
BTK signaling drives CD1d
Oncogene. 2019; 38(17):3316-3324 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
The immune microenvironment of pancreatic ductal adenocarcinoma (PDA) is comprised of a heterogeneous population of cells that are critical for disease evolution. Prominent among these are the specialized CD1d

Harada K, Ihara F, Takami M, et al.
Soluble factors derived from neuroblastoma cell lines suppress dendritic cell differentiation and activation.
Cancer Sci. 2019; 110(3):888-902 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Dendritic cells (DC) play a key role in the initiation of both antitumor immunity and immunological tolerance. It has been demonstrated that exposure to soluble factors produced by tumor cells modulates DC functions and induces tolerogenic DC differentiation. In this study, we investigated the effects of neuroblastoma cell line-derived soluble factors on DC differentiation. Monocytes isolated from healthy volunteers were incubated with interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor in the presence of culture supernatants from neuroblastoma cell lines. The culture supernatants from neuroblastoma cell lines, such as NLF and GOTO, partially blocked both downregulation of CD14 and upregulation of CD1a, and dramatically decreased IL-12 and tumor necrosis factor (TNF)-α production from mature DC, while no effect of SH-SY5Y cell supernatant was noted. In addition, IL-6 and IL-10 production from monocytes was increased by the supernatants of NLF and GOTO cells at 24 hours after incubation. Furthermore, we evaluated DC functions through stimulation of invariant natural killer T (iNKT) cells. α-Galactosylceramide-pulsed DC co-cultured with supernatants of NLF cells were unable to sufficiently stimulate iNKT cells. The decreased ability of iNKT cells to produce interferon (IFN)-γ after stimulation with neuroblastoma cell line supernatant-cultured DC was reversed by addition of IL-12. CD40 expression and IL-12 production in NLF-sup-treated DC were increased by addition of exogenous IFN-γ. These results indicate that tolerogenic DC are induced in the neuroblastoma tumor microenvironment and attenuate the antitumor effects of iNKT cells. Interactions between iNKT cells and αGalCer-pulsed DC have the potential to restore the immunosuppression of tolerogenic DC through IFN-γ production.

Chen S, Zhao Y, Shen F, et al.
Introduction of exogenous wild‑type p53 mediates the regulation of oncoprotein 18/stathmin signaling via nuclear factor‑κB in non‑small cell lung cancer NCI‑H1299 cells.
Oncol Rep. 2019; 41(3):2051-2059 [PubMed] Related Publications
Our previous studies demonstrated that high expression of oncoprotein 18 (Op18)/stathmin promotes malignant transformation of non‑small cell lung cancer NCI‑H1299 cells. Investigation of the cellular settings determined that NCI‑H1299 cells were genetically p53 deficient. In order to determine whether p53 deficiency is associated with Op18/stathmin‑mediated high levels of malignancy, exogenous wild‑type p53 (p53wt) was introduced into NCI‑H1299 cells in the present study to observe Op18/stathmin signaling changes and malignant behaviors. The results indicated that p53 downregulated Op18/stathmin expression and phosphorylation at the Ser25 and Ser63 sites in NCI‑H1299 cells, and the abilities of proliferation, colony formation and migration in multi‑dimensional spaces were simultaneously reduced. Introduction of p53wt inhibited the expression of the transcription factor nuclear factor‑κB (NF‑κB), and the activities of the Op18/stathmin upstream kinases cyclin‑dependent 2 (CDC2) and extracellular signal‑regulated kinase (ERK). Furthermore, blocking of NF‑κB signaling decreased CDC2 and ERK activation. Additionally, p53 intervention attenuated the secretion and protein expression of the immune inhibitory cytokine interleukin‑10, which was in accordance with the effect of NF‑κB signaling inhibition. Further experiments validated that p53 enhanced the sensitivity of NCI‑H1299 cells to Taxol through initiating the caspase‑3 and ‑9 intrinsic death pathways, and resulted in cell cycle arrest at the G1/S phases. These data indicated that exogenous p53wt mediates the regulation of Op18/stathmin signaling through the p53‑NF‑κB‑CDC2/ERK‑Op18/stathmin pathway, and that p53 deficiency is associated with high malignancy levels of NCI‑H1299 cells.

Moghmi M, Arjmandi A, Aghili K, et al.
Arq Bras Cir Dig. 2019; 32(1):e1415 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
INTRODUCTION: A series of studies have evaluated the association between -592A>C and -819T>C polymorphisms in the promoter regions of Interleukin-10 (IL-10) and gastric cancer (GC) risk. However, the results remain inconclusive.
OBJECTIVE: To better understand the association of the polymorphisms with GC risk, we performed a comprehensive meta-analysis.
METHOD: An electronic search was performed of several databases to identify relevant studies up to April 2018.
RESULTS: A total of 44 case-control studies, including 26 studies on IL-10 -592A>C (5,332 cases and 8,272 controls) and 18 studies on IL-10 -819T>C (3,431 cases and 6,109 controls) were selected. Overall, -592A>C polymorphism was associated with the risk of GC under the heterozygote model (OR=1.153, 95% CI=1.020-1.305, p=0.023), but not -819T>C polymorphism. When stratified by ethnicity, significant association was only observed in the Asians under the allele model (OR=1.153, 95% CI=1.007-1.320, p=0.040) and the heterozygote model (OR=1.218, 95% CI=1.076-1.379, p=0.002) for -592A>C.
CONCLUSION: The current meta-analysis results inconsistent with previous meta-analyses; showed that the IL-10 -592A>C polymorphism, but not -819T>C polymorphism, may be contributed to the susceptibility of GC in overall and Asian populations.

Matsui M, Kajikuri J, Kito H, et al.
Inhibition of Interleukin 10 Transcription through the SMAD2/3 Signaling Pathway by Ca
Mol Pharmacol. 2019; 95(3):294-302 [PubMed] Related Publications
The hyperpolarization induced by intermediate-conductance Ca

Li L, Ma Y, Xu Y
Follicular regulatory T cells infiltrated the ovarian carcinoma and resulted in CD8 T cell dysfunction dependent on IL-10 pathway.
Int Immunopharmacol. 2019; 68:81-87 [PubMed] Related Publications
A high Treg/CD8 T cell ratio in ovarian carcinoma was negatively associated with the prognosis of the patients. The human follicular regulatory T (Tfr) cells are a newly characterized subset of Treg cells with features of both follicular helper T (Tfh) cells (CXCR5

Mori S, Hickey A, Dusza SW, et al.
Markers of systemic involvement and death in hospitalized cancer patients with severe cutaneous adverse reactions.
J Am Acad Dermatol. 2019; 80(3):608-616 [PubMed] Article available free on PMC after 01/03/2020 Related Publications
BACKGROUND: Severe cutaneous adverse reactions (SCARs) are frequent in inpatient oncology. Early intervention might reduce morbidity, mortality, and hospitalization costs; however, current clinical and histologic features are unreliable SCAR predictors. There is a need to identify rational markers of SCARs that could lead to effective therapeutic interventions.
OBJECTIVE: To characterize the clinical and serologic features of hospitalized patients with cancer who developed SCARs.
METHODS: Retrospective review of 49 hospitalized cancer patients with a morbilliform rash, recorded testing for serum cytokines (interleukin [IL] 6, IL-10, and tumor necrosis factor [TNF] α) or elafin, and a prior dermatology consultation. Patients were categorized as having a simple morbilliform rash without systemic involvement or complex morbilliform rash with systemic involvement.
RESULTS: Fifteen out of 49 patients (30.6%) were deceased at 6 months from time of dermatologic consultation. Elafin, IL-6, and TNF-α were significantly higher in patients who died compared with patients who were still alive at 6 months. IL-6 and IL-10 were significantly higher in patients with a drug-related complex rash.
LIMITATIONS: Retrospective design, limited sample size, and high-risk patient population.
CONCLUSION: In cancer patients with SCARs, elafin, IL-6, and TNF-α levels might predict a poor outcome. Agents directed against these targets might represent rational treatments for the prevention of fatal SCARs.

Munteanu A, Munteanu D, Iancu M, et al.
Assessing immunological surgical stress markers in patients undergoing digestive surgery for pancreatic, hepatic and gastric tumors.
J BUON. 2018 Nov-Dec; 23(6):1655 [PubMed] Related Publications
PURPOSE: Cytokines like IL-6, IL-10 and other factors like CRP are involved in the postoperative inflammatory-stress response. The association between IL-6, IL-10, CRP, albumin and early postoperative complications and deaths was analyzed on a cohort of cancer patient.
METHODS: The plasma levels of IL-6, IL-10 and serum levels of c-reactive protein (CRP) and albumin were measured in 85 patients undergoing surgical resection of pancreatic, hepatic and gastric tumors. The measurement of the studied biochemical parameters was made at three time points: before the operation, and on the 1st and 3rd day after the operation.
RESULTS: Of the 85 patients, 28 suffered early postoperative complications (14 gastric cancer patients; 11 pancreatic cancer patients; 3 liver cancer patients) and 9 patients died in the early postoperative period (5 gastric cancer patients; 4 pancreatic cancer patients; 0 liver cancer patients). Patients with elevated levels of serum CRP on the 3rd postoperative day had a significant increased risk of death. Also, patients with higher levels of IL-10 on the 3rd postoperative day demonstrated a significantly increased risk of early postoperative complications.
CONCLUSION: This study demonstrates that plasma IL-10 concentration is positively associated with postoperative complications.

Daef EA, Elsherbiny NM, Agban MN, et al.
Bloodstream Infections in Febrile Neutropenic Pediatric Cancer Patients: Microbiological and Sepsis Biomarkers Insight.
Egypt J Immunol. 2018; 25(2):21-34 [PubMed] Related Publications
The diagnosis of blood steam infections (BSIs) in febrile neutropenic pediatric cancer patients (FNPCP) remains a challenge. Although blood culture is the most accurate method; yet the delay in results has urged the need for reliable biomarkers for early diagnosis. The objectives of this study were to identify the bacterial causes of BSIs in FNPCP at SECI and their antimicrobial susceptibility patterns. Also, to assess the value of procalcitonin (PCT), interleukin 6 (IL6), and interleukin 10 (IL 10) for early diagnosis of BSIs. This study included 68 FNPCP with a total of 85 fever episodes. Blood cultures were done at the onset of fever. Identification of the organisms was carried by Vitek 2 system and the antimicrobial susceptibility testing by disc diffusion. The levels of PCT, IL-6 and IL-10 serum levels were measured by ELISA. Blood stream bacterial infection was detected in 29.4% (25/85). Most were Gram positive cocci in 53.6 % (15/28). There were high percentages of multidrug resistant organism (MDRO) (73.3% and 92.3% among Gram positive and negative bacteria, respectively). The least percentage of resistance was to linezolid (0%) and amikacin (15.4%). The levels of the biomarkers were significantly higher in patients with positive bacterial cultures compared to those with negative cultures (P < 0.001). IL -6 had the best sensitivity (96%) (AUC 0.975, cut off 0.925ng/L) with considerable specificity (88.3%). Combined PCT & IL-6 had the highest sensitivity (96%) and specificity (98.3%). We conclude that the percentage of BSIs among FNPCP was considerable. Gram positive bacteria were the commonest causes. High percentages of MDRO were reported. The most efficient antimicrobials were linezolid and amikacin. IL-6 alone had the best sensitivity for early diagnosis of BSIs. The combination of PCT and IL 6 showed the best performance.

Lisiecka U, Kostro K, Dudek K, et al.
Evaluation of T regulatory lymphocytes and serum concentration of selected cytokines in dogs with perianal tumors.
Vet Immunol Immunopathol. 2019; 207:10-17 [PubMed] Related Publications
The purpose of this study was to determine concentrations of IL-2, IL-10, TGF-β1 in serum and T regulatory cell (Treg) percentage in peripheral blood of dogs with perianal tumours. Investigations were conducted on 32 male dogs of mixed breed. The animals were divided into 4 experimental groups and control group. The groups were established depending on the tumour malignancy degree and the type of dominant hormones. All measurements of serum cytokine concentrations were conducted by the use of commercial diagnostic ELISA kits. Treg lymphocyte percentage was measured by flow cytometry. In both groups with benign tumours cytokine levels decreased during therapy, whilst in groups with malignant tumors, in spite of applying anti-tumour therapy, concentrations of cytokines in serum markedly increased. The mean percentage of Treg lymphocytes in dogs with benign tumours (group I and II) was significantly lower than the mean percentage of these cells in control group at all time points, but after applying of anti-hormonal therapy, the significant increase of Treg percentage was observed compared to baseline values. By contrast, in both groups with malignant tumours (group III and IV), the mean percentage of Treg lymphocytes was significantly higher at the beginning of the experiment comparing with the control group as well as both groups with benign tumours and this percentage increased during anti-tumour therapy. The results of this study suggest that monitoring changes in cytokine serum concentrations and Treg percentage in the bloodstream during anti-hormonal therapy may constitute a subsidiary marker in the monitoring of therapy effectiveness, in prognosis the outcome of a disease or in differentiating tumour degree of malignancy.

Tipgomut C, Wongprommoon A, Takeo E, et al.
Melittin Induced G1 Cell Cycle Arrest and Apoptosis in Chago-K1 Human Bronchogenic Carcinoma Cells and Inhibited the Differentiation of THP-1 Cells into Tumour- Associated Macrophages
Asian Pac J Cancer Prev. 2018; 19(12):3427-3434 [PubMed] Article available free on PMC after 01/03/2020 Related Publications
Background: Bronchogenic carcinoma (lung cancer) is one of the leading causes of death. Although many compounds isolated from natural products have been used to treat it, drug resistance is a serious problem, and alternative anti-cancer drugs are required. Here, melittin from Apis mellifera venom was used, and its effects on bronchogenic carcinoma cell proliferation and tumour-associated macrophage differentiation were evaluated. Methods: The half maximal inhibitory concentration (IC50) of melittin was measured by MTT. Cell death was observed by annexin V and propidium iodide (PI) co-staining followed by flow cytometry. Cell cycle arrest was revealed by PI staining and flow cytometry. To investigate the tumour microenvironment, differentiation of circulating monocytes (THP-1) into tumour-associated macrophages (TAMs) was assayed by sandwich-ELISA and interleukin (IL)-10 levels were determined. Cell proliferation and migration was observed by flat plate colony formation. Secretion of vascular endothelial growth factor (VEGF) was detected by ELISA. The change in expression levels of CatS, Bcl-2, and MADD was measured by quantitative RT-PCR. Results: Melittin was significantly more cytotoxic (p < 0.01) to human bronchogenic carcinoma cells (ChaGo-K1) than to the control human lung fibroblasts (Wi-38) cells. At 2.5 μM, melittin caused ChaGo-K1 cells to undergo apoptosis and cell cycle arrest at the G1 phase. The IL-10 levels showed that melittin significantly inhibited the differentiation of THP-1 cells into TAMs (p < 0.05) and reduced the number of colonies formed in the treated ChaGo-K1 cells compared to the untreated cells. However, melittin did not affect angiogenesis in ChaGo-K1 cells. Unlike MADD, Bcl-2 was up-regulated significantly (p < 0.05) in melittin-treated ChaGo-K1 cells. Conclusion: Melittin can be used as an alternative agent for lung cancer treatment because of its cytotoxicity against ChaGo-K1 cells and the inhibition of differentiation of THP-1 cells into TAMs.

Moghimi M, Ahrar H, Karimi-Zarchi M, et al.
Association of IL-10 rs1800871 and rs1800872 Polymorphisms with Breast Cancer Risk: A Systematic Review and Meta-Analysis
Asian Pac J Cancer Prev. 2018; 19(12):3353-3359 [PubMed] Article available free on PMC after 01/03/2020 Related Publications
Background: The rs1800871 and rs1800872 polymorphisms of interleukin 10 (IL-10) gene has been indicated to be associated with breast cancer (BC) risk, but study results are still debatable. To derive a more precise evaluation, we performed a comprehensive meta-analysis. Methods: Multiple electronic databases were searched to identify studies assessing the IL-10 rs1800871 and rs1800872 polymorphisms with BC risk. Results: A total of 21 case-control studies with 6054 cases and 6355 controls were included in this met-analysis. There was a significant association between the rs1800871 polymorphism and BC risk (CT vs. TT: OR= 1.17, 95% CI 1.01-1.35, p=0.02; and CC+CT vs. TT: OR= 1.29, 95% CI 1.00-1.66, p=0.04). Moreover, increased BC risks were also associated with the rs1800872 polymorphism (C vs. A: OR= 1.29, 95% CI 1.04-1.60, p=0.01; CC vs. AA: OR= 1.54, 95% CI 1.03-2.30, p=0.03; CC+CA vs. AA: OR= 1.43, 95% CI 1.01-2.01, p=0.03; and CC vs. CA+AA: OR= 1.23, 95% CI 1.01-1.51, p=0.04). A pooling of the studies was also conducted by ethnicity, but failed to show an association of IL-10 rs1800871 and rs1800872 polymorphism with BC risk in Asians and Caucasians. Conclusions: Our results are inconsistent with previous meta-analysis suggests that IL-10 rs1800871 and rs1800872 polymorphisms might contribute to BC susceptibility in overall population, but not by ethnicity.

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