Caras Iuliana, Tucureanu Catalin, Lerescu Lucian, Pitica Ramona, Melinceanu Laura, Neagu Stefan, Salageanu Aurora
Infection and Immunity Laboratory, National Institute for Research and Development in Microbiology and Immunology Cantacuzino, 103 Spl Independentei, sector 5, 050096 Bucharest, Romania.
Tumori. 2011 Sep-Oct;97(5):647-54. doi: 10.1177/030089161109700518.
Macrophages are heterogeneous cells with extensive functional plasticity; they can change their functional profiles repeatedly in response to environmental changes anywhere between their extreme phenotypical programs (labeled as M1 and M2 polarization, respectively). In terms of antitumoral immune response, M1 macrophages are considered to be beneficial, while M2 macrophages supposedly promote tumor progression. Tumor-associated macrophages (TAMs) represent a major leukocyte population present in many tumors. Although many studies indicate that TAMs elicit several M2-associated protumoral functions, including promotion of angiogenesis, matrix remodeling and suppression of adaptive immunity, their role regarding tumor progression is still controversial. The aim of the present study was to develop an appropriate in vitro model to study the effect of tumor-secreted soluble factors on the functional phenotype of macrophages.
THP-1 human monocytic line cells and peripheral blood mononuclear cells from healthy volunteers were used for macrophage differentiation; primary tumor cell culture supernatants or tumor cell line supernatants were employed along with various cytokines, growth factors and other stimuli to design different model variants and to better mimic the in vivo tumor microenvironment.
The cytokine secretion patterns of these macrophages suggest that primary tumor cell culture supernatants are able to switch the macrophage phenotype or to induce functional polarization of macrophages toward a mixed M1/M2 phenotype. Conclusions. These data support the hypothesis that TAM behavior is modulated by the tumor microenvironment itself.
巨噬细胞是具有广泛功能可塑性的异质性细胞；它们能够在其极端表型程序（分别标记为M1和M2极化）之间的任何环境变化下反复改变其功能谱。在抗肿瘤免疫反应方面，M1巨噬细胞被认为是有益的，而M2巨噬细胞则被认为会促进肿瘤进展。肿瘤相关巨噬细胞（TAM）是许多肿瘤中存在的主要白细胞群体。尽管许多研究表明TAM具有多种与M2相关的促肿瘤功能，包括促进血管生成、基质重塑和抑制适应性免疫，但其在肿瘤进展中的作用仍存在争议。本研究的目的是建立一个合适的体外模型，以研究肿瘤分泌的可溶性因子对巨噬细胞功能表型的影响。
使用THP - 1人单核细胞系细胞和健康志愿者的外周血单核细胞进行巨噬细胞分化；使用原代肿瘤细胞培养上清液或肿瘤细胞系上清液以及各种细胞因子、生长因子和其他刺激物来设计不同的模型变体，以更好地模拟体内肿瘤微环境。
这些巨噬细胞的细胞因子分泌模式表明，原代肿瘤细胞培养上清液能够改变巨噬细胞表型或诱导巨噬细胞向混合M1/M2表型的功能极化。结论。这些数据支持TAM行为受肿瘤微环境本身调节的假设。
