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首页> 外文期刊>Journal of immunotherapy >Systemic immune tuning in renal cell carcinoma: favorable prognostic impact of TGF-beta1 mRNA expression in peripheral blood mononuclear cells.
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Systemic immune tuning in renal cell carcinoma: favorable prognostic impact of TGF-beta1 mRNA expression in peripheral blood mononuclear cells.

机译：肾细胞癌的全身免疫调节：外周血单个核细胞中TGF-beta1 mRNA表达的有利预后影响。

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Renal cell carcinoma (RCC) can inhibit protective immunity by induction of immunosuppressive cells that produce inhibitory cytokines such as interleukin (IL)-10 and transforming growth factor (TGF)-beta. If this immunosuppression influences response to kinase inhibitors such as sorafenib is not known. Therefore, we asked for the prognostic influence of cells with immunosuppressive properties in peripheral blood (pB) in a cohort of metastatic clear cell renal cell carcinoma (mRCC) patients uniformly receiving sorafenib treatment. IL-10 and TGF-beta mRNA levels, regulatory T-cell (Treg) counts, and frequencies of IL-10/TGF-beta producing mononuclear cell subsets were determined in pB from 46 patients with mRCC before receiving sorafenib treatment. Relationship between established clinical and laboratory prognostic factors and outcome were examined by univariate and multivariate Cox regression analysis. IL-10 and TGF-beta1 mRNA levels, and frequencies of CD4(+)CD25high/CD3(+) and CD4(+)CD25highFoxP3(+)/CD3(+)Treg cells were significantly higher in mRCC patients compared with healthy individuals. Monocytes were suggested as main producers of IL-10 and TGF-beta. In a multivariate analysis low ECOG score and-surprisingly-high TGF-beta1 mRNA levels were independently associated with favorable progression-free survival (P=0.005 and P=0.003, respectively) and overall survival (P=0.001 and P=0.039, respectively). In conclusion, mRCC is associated with an immunosuppressive phenotype in peripheral blood. The positive prognostic influence of high TGF-beta1 mRNA expression levels may reflect immune promoting functions of TGF-beta in combined activity with inflammatory cytokines.
机译：肾细胞癌（RCC）可以通过诱导产生抑制性细胞因子（例如白介素（IL）-10和转化生长因子（TGF）-β）的免疫抑制细胞来抑制保护性免疫。这种免疫抑制是否会影响对激酶抑制剂（例如索拉非尼）的反应。因此，我们询问了接受统一治疗索拉非尼治疗的转移性透明细胞肾细胞癌（mRCC）患者队列中外周血（pB）具有免疫抑制特性的细胞的预后影响。在接受索拉非尼治疗之前，从46名患有mRCC的患者的pB中确定了IL-10和TGF-βmRNA水平，调节性T细胞（Treg）计数以及产生IL-10 /TGF-β的单核细胞亚群的频率。通过单因素和多因素Cox回归分析检查已建立的临床和实验室预后因素与预后之间的关系。与健康个体相比，mRCC患者的IL-10和TGF-beta1 mRNA水平以及CD4（+）CD25high / CD3（+）和CD4（+）CD25highFoxP3（+）/ CD3（+）Treg细胞的频率明显更高。建议将单核细胞作为IL-10和TGF-β的主要产生者。在多变量分析中，低ECOG评分和令人惊讶的高TGF-beta1 mRNA水平分别与良好的无进展生存期（分别为P = 0.005和P = 0.003）和总生存期（分别为P = 0.001和P = 0.039）相关。 ）。总之，mRCC与外周血中的免疫抑制表型有关。高TGF-beta1 mRNA表达水平的积极预后影响可能反映了TGF-beta与炎性细胞因子联合活动的免疫促进功能。

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