Polymorphism of IL‐10 receptor β affects the prognosis of multiple myeloma patients treated with thalidomide and/or bortezomib

Kasamatsu, Tetsuhiro; Saitoh, Takayuki; Ino, Rumi; Gotoh, Nanami; Mitsui, Takeki; Shimizu, Hiroaki; Matsumoto, Morio; Sawamura, Morio; Yokohama, Akihiko; Handa, Hiroshi; Tsukamoto, Norifumi; Murakami, Hirokazu

doi:10.1002/hon.2322

Cited by 10 publications

(8 citation statements)

References 33 publications

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“…Moreover, differences in survival were observed between subjects treated with thalidomide and/or bortezomib and those cured with conventional drugs. Their results suggest that IL-10 and IL-10R gene polymorphisms may not influence the predisposition to MM but may be correlated with the severity and prognosis of MM [ 212 ].…”

Section: Anti-inflammatory Cytokinesmentioning

confidence: 99%

Inflammatory and Anti-Inflammatory Equilibrium, Proliferative and Antiproliferative Balance: The Role of Cytokines in Multiple Myeloma

Musolino

Allegra

Innao

et al. 2017

Mediators of Inflammation

119

113

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Multiple myeloma (MM) is typically exemplified by a desynchronized cytokine system with increased levels of inflammatory cytokines. We focused on the contrast between inflammatory and anti-inflammatory systems by assessing the role of cytokines and their influence on MM. The aim of this review is to summarize the available information to date concerning this equilibrium to provide an overview of the research exploring the roles of serum cytokines in MM. However, the association between MM and inflammatory cytokines appears to be inadequate, and other functions, such as pro-proliferative or antiproliferative effects, can assume the role of cytokines in the genesis and progression of MM. It is possible that inflammation, when guided by cancer-specific Th1 cells, may inhibit tumour onset and progression. In a Th1 microenvironment, proinflammatory cytokines (e.g., IL-6 and IL-1) may contribute to tumour eradication by attracting leucocytes from the circulation and by increasing CD4 + T cell activity. Hence, caution should be used when considering therapies that target factors with pro-or anti-inflammatory activity. Drugs that may reduce the tumour-suppressive Th1-driven inflammatory immune response should be avoided. A better understanding of the relationship between inflammation and myeloma will ensure more effective therapeutic interventions.

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Section: Anti-inflammatory Cytokinesmentioning

confidence: 99%

Inflammatory and Anti-Inflammatory Equilibrium, Proliferative and Antiproliferative Balance: The Role of Cytokines in Multiple Myeloma

Musolino

Allegra

Innao

et al. 2017

Mediators of Inflammation

119

113

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“…IL-10 is a cytokine that regulates immune function, acting on a variety of immune cell subsets and playing a role in immune suppression in a variety of ways that can cause or prevent tumor immune escape. Recent studies reported that IL-10 also stimulates the immune response, suggesting that it is a multifunctional cytokine with positive and negative regulatory effects [24].…”

Section: Discussionmentioning

confidence: 99%

The suppressive effect of co-inhibiting PD-1 and CTLA-4 expression on H22 hepatomas in mice

Liang

Zhang

2018

Cell Mol Biol Lett

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ObjectiveWe investigated the suppressive effect of siRNA-mediated co-inhibition of PD-1 and CTLA-4 expression on H22 hepatomas in mice.MethodsMurine H22 cells were cultured in vivo in ICR mice. An allograft tumor model was also established in another ICR mouse group. The tumor-bearing mice were randomly divided into four groups: control, single PD-1 siRNA, single CTLA-4 siRNA, and double PD-1 + CTLA-4 siRNAs. The survival time and physiological condition of the mice were observed after the injection of the siRNAs and placebo. The volume and weight of the solid tumor were measured to assess the inhibition of the tumor. To assess the effects of siRNAs on mouse immune function, the protein levels of IFN-γ and IL-10 in the blood and PD-L1 in the tumor and liver were determined using ELISA, and the mRNA levels of IFN-γ, PD-L1, PD-1, CTLA-4, IL-6 and Survivin in the tumor, liver and spleen were determined using quantitative RT-PCR. The ratios of Bax and Bcl-2 protein were determined via western blot to analyze the effect of siRNAs on tumor cell apoptosis.ResultsThe anti-tumor effect appeared in all groups with siRNA-mediated inhibition. The tumor growth suppression was stronger in the group with double inhibition. The weight and volume of the tumors were significantly lower and the survival rate improved in the three siRNA groups. IFN-γ levels increased but IL-10 levels decreased in the blood of the siRNA group mice compared with the results for the control group. In the tumor and spleen tissue, the IFN-γ levels significantly increased, but in the liver tissue they significantly decreased in the three siRNA groups. The results of quantitative RT-PCR showed that the mRNAs for PD-1 and CTLA-4 were downregulated in spleen tissue in the three siRNA groups, while the PD-L1 mRNA and protein levels increased significantly in the tumor, but decreased in the liver. Survivin and IL-6 mRNA levels decreased in the tumor. Western blot results showed that ratio of Bax and Bcl-2 had significantly increased. These results indicated that downregulating PD-1 and CTLA-4 could increase the body’s immune response and promote apoptosis of tumor cells.ConclusionCo-inhibiting the expressions of PD-1 and CTLA-4 can effectively suppress the growth of H22 hepatoma and promote the apoptosis of tumor cells in mice. Blocking PD-1 and CTLA-4 can improve the vitality of T cells, and improve the immune environment and response.

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“…The published dates of all research studies varied from 2000 to 2018. Most of the research was conducted within Caucasian communities: 10 studies in Caucasian populations (62.5%) (20,22,23,25,(33)(34)(35)(36)(37)(38), 3 within Asian populations (18.75%) (17,39,40) and 3 in Mixed Afro-American populations (18.75%) (24,41,42). Of note, the quantitative TaqMan method (TaqMan PCR) was often used to detect the SNP state with control references (11 studies, 68.75%) (20,(22)(23)(24)(25)(36)(37)(38)(39)41,42).…”

Section: Study Selectionmentioning

confidence: 99%

“…Of note, the quantitative TaqMan method (TaqMan PCR) was often used to detect the SNP state with control references (11 studies, 68.75%) (20,(22)(23)(24)(25)(36)(37)(38)(39)41,42). Also, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used in 5 studies (31.25%) (17,(33)(34)(35)40). The variables from sixteen relevant case-control studies were contained 2,597 cases and 3,851 controls.…”

Section: Study Selectionmentioning

confidence: 99%

“…The variables from sixteen relevant case-control studies were contained 2,597 cases and 3,851 controls. Source controls were mainly selected by population-based method with age/sex-matched (12 studies, 75%) (17,20,(23)(24)(25)33,34,36,38,(40)(41)(42). Regarding the NOS methodological quality, all included studies were of high quality with ≥7 out of 10 (mean 8.02 point).…”

Section: Study Selectionmentioning

confidence: 99%

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Association between interleukin gene polymorphisms and multiple myeloma susceptibility

et al. 2020

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The present study performed a retrospective observational study in order to investigate the relationship between the interleukin family gene polymorphisms and risk of multiple myeloma (MM), based on sixteen case-control studies that contained 2,597 patients with MM and 3,851 controls. The results demonstrated that the genotypes IL-6 and IL-1 GG increased the risk of MM by approximately 40.8 and 80.2% compared with the genotypes AA and CC [odds ratio (OR)=1.14, 95% confidence interval (CI), 0.88-1.47, and OR=1.16, 95% CI, 0.61-2.19; respectively]. The results also revealed a significant association between T:C polymorphism of the IL-6 and IL-10 and the risk of MM (TC/CC: OR=1.37, 95% CI, 0.88-2.16 and TT/CC: OR=1.26, 95% CI, 0.77-2.06, respectively). Additionally, no significant association was identified between the C:A polymorphisms of the IL-6 (rs8192284) and IL-10 (rs1800872) receptors and the overall risk of MM (P>0.05). G:C polymorphisms of the IL-1β1464G>C and IL-6572G>C significantly increased the risk of MM (P<0.05). However, it has been determined that there is a significant association between the C:T polymorphism of the IL-1α-889C>T and IL-1β-3737C>T and the risk of MM (P<0.001). Subgroup analysis revealed that the detection of G:A polymorphisms in the IL-6 promoter (OR=1.05, 95% CI, 0.78-1.44) is more accurate in MM samples of the Asian population (OR=1.24, 95% CI, 0.92-1.74). In addition, no significant association was identified between the IL gene polymorphisms in MM samples categorized by ethnicity and the IL family type (P=0.27). These single nucleotide polymorphism loci may be the appropriate gene markers for gene screening and a promising therapeutic strategy in the prognostics of patients with MM.

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Polymorphism of IL‐10 receptor β affects the prognosis of multiple myeloma patients treated with thalidomide and/or bortezomib

Cited by 10 publications

References 33 publications

Inflammatory and Anti-Inflammatory Equilibrium, Proliferative and Antiproliferative Balance: The Role of Cytokines in Multiple Myeloma

Inflammatory and Anti-Inflammatory Equilibrium, Proliferative and Antiproliferative Balance: The Role of Cytokines in Multiple Myeloma

The suppressive effect of co-inhibiting PD-1 and CTLA-4 expression on H22 hepatomas in mice

Association between interleukin gene polymorphisms and multiple myeloma susceptibility

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