来源于儿科恶性肿瘤的肿瘤间质细胞表现出 MSC 样特性，并损害 NK 细胞的细胞毒性。

BACKGROUND

Tumour growth and metastatic infiltration are favoured by several components of the tumour microenvironment. Bone marrow-derived multipotent mesenchymal stromal cells (MSC) are known to contribute to the tumour stroma. When isolated from healthy bone marrow, MSC exert potent antiproliferative effects on immune effector cells. Due to phenotypic and morphological similarities of MSC and tumour stromal cells (TStrC), we speculated that immunotherapeutic approaches may be hampered if TStrC may still exhibit immunomodulatory properties of MSC.

METHODS

In order to compare immunomodulatory properties of MSC and tumour stromal cells (TStrC), we established and analyzed TStrC cultures from eleven paediatric tumours and MSC preparations from bone marrow aspirates. Immunophenotyping, proliferation assays and NK cell cytotoxicity assays were employed to address the issue.

RESULTS

While TStrC differed from MSC in terms of plasticity, they shared surface expression of CD105, CD73 and other markers used for MSC characterization. Furthermore, TStrC displayed a strong antiproliferative effect on peripheral blood mononuclear cells (PBMC) in coculture experiments similar to MSC. NK cell cytotoxicity was significantly impaired after co-culture with TStrC and expression of the activating NK cell receptors NKp44 and NKp46 was reduced.

CONCLUSIONS

Our data show that TStrC and MSC share important phenotypic and functional characteristics. The inhibitory effect of TStrC on PBMC and especially on NK cells may facilitate the immune evasion of paediatric tumours.

背景

肿瘤生长和转移浸润受到肿瘤微环境的多个成分的影响。骨髓来源的多能间充质基质细胞（MSC）已知有助于肿瘤基质的形成。当从健康骨髓中分离出来时，MSC 对免疫效应细胞具有强烈的抗增殖作用。由于 MSC 和肿瘤基质细胞（TStrC）之间存在表型和形态学上的相似性，我们推测如果 TStrC 仍然具有 MSC 的免疫调节特性，免疫治疗方法可能会受到阻碍。

方法

为了比较 MSC 和肿瘤基质细胞（TStrC）的免疫调节特性，我们从 11 例儿科肿瘤中建立和分析了 TStrC 培养物，并从骨髓抽吸物中建立和分析了 MSC 制剂。采用免疫表型分析、增殖实验和 NK 细胞细胞毒性实验来解决这个问题。

结果

虽然 TStrC 在可塑性方面与 MSC 不同，但它们在表面表达 CD105、CD73 和其他用于 MSC 特征描述的标记物方面存在相似性。此外，在共培养实验中，TStrC 对外周血单核细胞（PBMC）表现出强烈的抗增殖作用，与 MSC 相似。NK 细胞的细胞毒性在与 TStrC 共培养后显著受损，并且激活 NK 细胞受体 NKp44 和 NKp46 的表达减少。