Background/Objectives: Macrophages with the M2 phenotype are an immune population with great relevance for tumor development. We have previously demonstrated that mesenchymal stromal cells (MSCs) from cervical cancer (CeCa-MSCs) enhance the immunomodulatory activity of CeCa cells on T lymphocytes; however, the effect of these cells on the ability of tumor cells to polarize macrophages had not been evaluated to date. Methods: To address this, we set out to analyze the effect of normal cervix (NCx) and CeCa-MSCs interacting with CeCa tumor cells (TCs) to polarize macrophages in a coculture system. Results: Our results show that macrophages from TC/NCx-MSC cocultures decreased CD163 expression. In turn, we observed that macrophages from TC/CeCa-MSC cocultures, in contrast to those in the presence of TCs/NCx-MSCs, increased the intracellular production of IDO, IL-4, and IL-10; decreased T lymphocyte proliferation; and increased the presence of soluble IL-10. Interestingly, coculture in the presence of TCs/NCx-MSCs decreased the capacity of macrophages to generate regulatory T lymphocyte populations, as well as their phagocytic capacity, and increased IL-6 secretion, unlike the coculture of macrophages in the presence of TCs/CeCa-MSCs. Our results show that TCs/CeCa-MSCs in cocultures, unlike TCs/NCx-MSCs, have a greater capacity to polarize macrophages to an M2 phenotype and that such macrophages have a greater immunosuppressive potential. Conclusions: This in vitro study suggests that intracellular communication between MSCs and tumor cells in CeCa may promote tumor growth through the polarization of macrophages with increased immunosuppressive activity.
背景/目的:M2表型巨噬细胞是与肿瘤发展密切相关的免疫群体。我们先前已证实,宫颈癌间充质基质细胞(CeCa-MSCs)能增强宫颈癌细胞对T淋巴细胞的免疫调节活性;然而,这些细胞对肿瘤细胞极化巨噬细胞能力的影响迄今尚未得到评估。方法:为探究此问题,我们通过共培养系统分析正常宫颈(NCx)与CeCa-MSCs分别与宫颈癌肿瘤细胞(TCs)相互作用对巨噬细胞极化的影响。结果:研究发现,TC/NCx-MSC共培养组中的巨噬细胞CD163表达降低。相比之下,TC/CeCa-MSC共培养组中的巨噬细胞在IDO、IL-4和IL-10的胞内生成方面显著增加,同时抑制T淋巴细胞增殖并促进可溶性IL-10的释放。值得注意的是,与TC/CeCa-MSC共培养组不同,TC/NCx-MSC共培养条件下的巨噬细胞不仅降低了诱导调节性T淋巴细胞群的能力及吞噬功能,还增加了IL-6的分泌。实验结果表明,相较于TC/NCx-MSCs,TC/CeCa-MSCs在共培养体系中具有更强的巨噬细胞M2表型极化能力,且此类巨噬细胞表现出更强的免疫抑制潜能。结论:本体外研究表明,宫颈癌中MSCs与肿瘤细胞间的胞内通讯可能通过极化具有增强免疫抑制活性的巨噬细胞来促进肿瘤生长。