Liotta F, Querci V, Mannelli G, Santarlasci V, Maggi L, Capone M, Rossi M C, Mazzoni A, Cosmi L, Romagnani S, Maggi E, Gallo O, Annunziato F
1] Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence, 50134 Florence, Italy [2] Regenerative Medicine Unit and Immunology and Cellular Therapy Unit of Azienda Ospedaliero-Universitaria Careggi, 50134 Florence, Italy.
Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence, 50134 Florence, Italy.
Br J Cancer. 2015 Feb 17;112(4):745-54. doi: 10.1038/bjc.2015.15. Epub 2015 Feb 3.
Cancer is a multifactorial disease not only restricted to transformed epithelium, but also involving cells of the immune system and cells of mesenchymal origin, particularly mesenchymal stem cells (MSCs). Mesenchymal stem cells contribute to blood- and lymph- neoangiogenesis, generate myofibroblasts, with pro-invasive activity and may suppress anti-tumour immunity.
In this paper, we evaluated the presence and features of MSCs isolated from human head neck squamous cell carcinoma (HNSCC).
Fresh specimens of HNSCC showed higher proportions of CD90+ cells compared with normal tissue; these cells co-expressed CD29, CD105, and CD73, but not CD31, CD45, CD133, and human epithelial antigen similarly to bone marrow-derived MSCs (BM-MSCs). Adherent stromal cells isolated from tumour shared also differentiation potential with BM-MSCs, thus we named them as tumour-MSCs. Interestingly, tumour-MSCs showed a clear immunosuppressive activity on in vitro stimulated T lymphocytes, mainly mediated by indoelamine 2,3 dioxygenase activity, like BM-MSCs. To evaluate their possible role in tumour growth in vivo, we correlated tumour-MSC proportions with neoplasm size. Tumour-MSCs frequency directly correlated with tumour volume and inversely with the frequency of tumour-infiltrating leukocytes.
These data support the concept that tumour-MSCs may favour tumour growth not only through their effect on stromal development, but also by inhibiting the anti-tumour immune response.
癌症是一种多因素疾病,不仅局限于转化的上皮细胞,还涉及免疫系统细胞和间充质来源的细胞,特别是间充质干细胞(MSC)。间充质干细胞促进血液和淋巴新生血管生成,产生具有促侵袭活性的肌成纤维细胞,并可能抑制抗肿瘤免疫。
在本文中,我们评估了从人头颈部鳞状细胞癌(HNSCC)中分离出的间充质干细胞的存在情况和特征。
与正常组织相比,HNSCC新鲜标本显示CD90+细胞比例更高;这些细胞与骨髓来源的间充质干细胞(BM-MSC)类似,共表达CD29、CD105和CD73,但不表达CD31、CD45、CD133和人上皮抗原。从肿瘤中分离出的贴壁基质细胞也与BM-MSC具有相同的分化潜能,因此我们将它们命名为肿瘤-MSC。有趣的是,肿瘤-MSC对体外刺激的T淋巴细胞表现出明显的免疫抑制活性,主要由吲哚胺2,3双加氧酶活性介导,与BM-MSC类似。为了评估它们在体内肿瘤生长中的可能作用,我们将肿瘤-MSC比例与肿瘤大小进行了关联。肿瘤-MSC频率与肿瘤体积直接相关,与肿瘤浸润白细胞频率呈负相关。
这些数据支持这样的概念,即肿瘤-MSC可能不仅通过其对基质发育的影响,还通过抑制抗肿瘤免疫反应来促进肿瘤生长。