Tumor-associated leukemia inhibitory factor and IL-6 skew monocyte differentiation into tumor-associated macrophage-like cells
Tumor-associated leukemia inhibitory factor and IL-6 skew monocyte differentiation into tumor-associated macrophage-like cells
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DOI：
10.1182/blood-2007-02-072587
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发表时间：
2007-12-15
期刊：
影响因子：
20.3
通讯作者：
Jeannin, Pascale
中科院分区：
文献类型：
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作者：
Duluc, Dorothee;Delneste, Yves;Jeannin, Pascale
肿瘤相关巨噬细胞(TAMs)是肿瘤微环境中含量最丰富的免疫抑制细胞，来源于外周血单核细胞，表现为IL-10(高)、IL-12(低)M2谱。这一代所涉及的因素尚不清楚。在此，我们确定白血病抑制因子和IL-6是促进生成的肿瘤微环境因子。卵巢癌腹水使单核细胞分化为样细胞，表现出大部分卵巢的功能和表型特征。卵巢癌腹水中含有高浓度的LIF和IL-6。重组LIF和IL-6通过单核细胞吞噬单核细胞集落刺激因子(M-CSF)诱导单核细胞向样细胞分化。卵巢癌腹水中LIF、IL-6和M-CSF的缺失抑制了样细胞的诱导。我们将这些观察扩展到不同的肿瘤细胞系上清液。这些发现不仅揭示了通过LIF和IL-6产生的新的肿瘤逃逸机制，而且为颠覆诱导的免疫抑制从而提高基于T细胞的抗肿瘤免疫治疗效果提供了新的治疗视角。
Tumor-associated macrophages (TAMs), the most abundant immunosuppressive cells in the tumor microenvironment, originate from blood monocytes and exhibit an IL-10(high)IL-12(low) M2 profile. The factors involved in TAM generation remain unidentified. We identify here leukemia inhibitory factor (LIF) and IL-6 as tumor microenvironmental factors that can promote TAM generation. Ovarian cancer ascites switched monocyte differentiation into TAM-like cells that exhibit most ovarian TAM functional and phenotypic characteristics. Ovarian cancer ascites contained high concentrations of LIF and IL-6. Recombinant LIF and IL-6 skew monocyte differentiation into TAM-like cells by enabling monocytes to consume monocyte-colony-stimulating factor (M-CSF). Depletion of LIF, IL-6, and M-CSF in ovarian cancer ascites suppressed TAM-like cell induction. We extended these observations to different tumor-cell line supernatants. In addition to revealing a new tumor-escape mechanism associated with TAM generation via LIF and IL-6, these findings offer novel therapeutic perspectives to subvert TAM-induced immunosuppression and hence improve T-cell-based antitumor immunotherapy efficacy.