TGFβ is responsible for skin tumour infiltration by macrophages enabling the tumours to escape immune destruction
TGFβ is responsible for skin tumour infiltration by macrophages enabling the tumours to escape immune destruction
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DOI：
10.1038/sj.icb.7100116
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发表时间：
2008-01-01
影响因子：
4
通讯作者：
Halliday, Gary M.
中科院分区：
文献类型：
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作者：
Byrne, Scott N.;Knox, Matthew C.;Halliday, Gary M.
巨噬细胞对皮肤肿瘤的浸润是肿瘤进展中的重要步骤，尽管巨噬细胞募集到肿瘤块的机制以及随后对肿瘤生长的影响知之甚少。用转化生长因子（TGF）β基因转染小鼠退行性皮肤肿瘤，使肿瘤在体内逐渐生长，从而使我们能够研究这种细胞因子在肿瘤生长中的作用。流式细胞术显示TGF β介导的肿瘤进展伴随着肿瘤相关巨噬细胞（TAM）的增加和肿瘤浸润树突状细胞（DC）的减少。TAM在TGF β-分泌肿瘤中表达较低水平的主要组织相容性复合物II和CD 86相比，在控制肿瘤中的DC，并具有高吞噬能力，所测量的乳胶珠在体内的摄取。事实上，TGF β不仅直接负责增强的巨噬细胞吞噬作用，而且还改变了抗原呈递细胞的比例，使巨噬细胞优于DC。我们的研究结果表明，TGFb的招募和巨噬细胞在肿瘤部位的保留能够有效地逃避宿主免疫系统的肿瘤，并加强了在人类癌症免疫治疗试验中靶向TGFb的需要。
Infiltration of skin tumours by macrophages is an important step in tumour progression, although the mechanisms of macrophage recruitment to the tumour mass and the subsequent effects on tumour growth are poorly understood. Transfecting a murine regressing skin tumour with the gene for transforming growth factor (TGF)beta enabled the tumours to grow progressively in vivo thus allowing us to study the role of this cytokine in tumour growth. Flow cytometry was used to show that TGF beta-mediated tumour progression was accompanied by an increase in tumour-associated macrophages (TAM) and a decrease in tumour-infiltrating dendritic cells (DCs). TAM in TGFb-secreting tumours expressed lower levels of major histocompatibility complex II and CD86 compared to DC in control tumours and had a high phagocytic capacity as measured by uptake of latex beads in vivo. Indeed, TGF beta was directly responsible not only for the enhanced macrophage phagocytosis but also altering the ratio of antigen-presenting cells to favour macrophages over DC. Our results demonstrate that TGFb recruitment and retention of macrophages at the tumour site enable effective tumour evasion of the host immune system and reinforces the need to target TGFb in human cancer immunotherapy trials.