Pilatova K, Budinská E, Bensciková B, Nenutil R, Šefr R, Fedorová L, Hanáková B, Brychtová V, Zdražilová Dubská L
Klin Onkol. 2017 Spring;30(Supplementum1):166-169.
Myeloid-derived suppressor cells (MDSCs) are heterogenic population of multipotent progenitors of myeloid lineage. For their immunosuppressive effect, MDSC are responsible for tumour escape from the host immune surveillance. Furthermore, MDSCs support tumour by promotion of angiogenesis and metastasis. Membrane markers of human MDSCs are myeloid markers CD11b and CD13, these cells are HLA-Drlow/- and expression of CD15 or CD14 differentiate them into granulocytic (Gr-MDSCs) and monocytic (Mo-MDSCs), resp.
Using flow cytometry, we investigated Mo-MDSC counts in peripheral blood of non-cancer individuals - control group (n = 61), breast (n = 39) and colorectal (n = 52) cancer patients. These cells were detected as CD45+CD11b+CD33+CD14+HLA-Drlow/- and quantified as percentage of total white blood cells and as absolute count.
In control group, circulating Mo-MDSCs was gender-and age-independent and the average value was 1.09% and 0.073 × 109/l. Breast cancer patients had higher circulating Mo-MDSCs compared to control group with average values: 3.57% and 0.229 × 109/l (p < 0.001) and we also observed increase in Mo-MDSC number after granulopoietic growth factors administration (p = 0.043). Colorectal cancer patients had higher average number of circulating Mo-MDSCs compared to control group: 1.71% a 0.125 × 109/l (p = 0.003) and its number did not correlate with tumour clinicopathological stage, localization of primary tumour (colon vs. rectum), site (left vs. right) and microsatellite instability.
Increased number of MDSCs in circulation and within tumour microenvironment has been associated with immune suppression and tumour progression. Colorectal cancer patients at diagnosis showed higher circulating Mo-MDSCs possibly reflecting immunosuppressive effect of tumour microenvironment. Change of Mo-MDSC number from baseline level need to be evaluated in the context of CRC patients outcome. Recombinant granulopoietic growth factors increase number of circulating Mo-MDSCs and the effect of this phenomenon on cancer prognosis remains to be elucidated.Key words: myeloid-derived suppressor cells - colorectal cancer - breast cancer - immunology - immunosuppression - G-CSF This work was supported by MEYS by NPU I (LO1413), grant AZV 16-31966A and MH DRO 00209805. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 11. 3. 2017Accepted: 26. 3. 2017.
髓系来源的抑制性细胞(MDSCs)是髓系谱系多能祖细胞的异质性群体。由于其免疫抑制作用,MDSC 导致肿瘤逃避宿主免疫监视。此外,MDSCs 通过促进血管生成和转移来支持肿瘤生长。人类 MDSCs 的膜标志物是髓系标志物 CD11b 和 CD13,这些细胞 HLA-Dr 低表达/不表达,CD15 或 CD14 的表达分别将它们分化为粒细胞性(Gr-MDSCs)和单核细胞性(Mo-MDSCs)。
我们使用流式细胞术研究了非癌症个体(对照组,n = 61)、乳腺癌患者(n = 39)和结直肠癌患者(n = 52)外周血中 Mo-MDSC 的数量。这些细胞被检测为 CD45+CD11b+CD33+CD14+HLA-Dr 低表达/不表达,并作为总白细胞的百分比和绝对计数进行量化。
在对照组中,循环中的 Mo-MDSCs 与性别和年龄无关,平均值分别为 1.09%和 0.073×10⁹/L。与对照组相比,乳腺癌患者循环中的 Mo-MDSCs 更高,平均值分别为 3.57%和 0.229×10⁹/L(p < 0.001),并且我们还观察到给予粒细胞生成生长因子后 Mo-MDSC 数量增加(p = 0.043)。与对照组相比,结直肠癌患者循环中的 Mo-MDSCs 平均数量更高:1.71%和 0.125×10⁹/L(p = 0.003),其数量与肿瘤临床病理分期、原发性肿瘤定位(结肠与直肠)、部位(左侧与右侧)和微卫星不稳定性无关。
循环中和肿瘤微环境中 MDSCs 数量的增加与免疫抑制和肿瘤进展相关。结直肠癌患者在诊断时显示出较高的循环 Mo-MDSCs,这可能反映了肿瘤微环境的免疫抑制作用。需要在结直肠癌患者的预后背景下评估 Mo-MDSC 数量相对于基线水平的变化。重组粒细胞生成生长因子增加了循环 Mo-MDSCs 的数量,这种现象对癌症预后的影响仍有待阐明。关键词:髓系来源的抑制性细胞 - 结直肠癌 - 乳腺癌 - 免疫学 - 免疫抑制 - G-CSF 本研究得到了 MEYS 的 NPU I(LO1413)、AZV 16 - 31966A 资助以及 MH DRO 00209805 的支持。作者声明他们在研究中使用的药物、产品或服务方面没有潜在的利益冲突。编辑委员会声明该手稿符合 ICMJE 对生物医学论文的建议。提交日期:2017 年 3 月 11 日。接受日期:2017 年 3 月 26 日。