Department of Radiation Oncology, Emory University School of Medicine Atlanta GA USA 30322.
Am J Cancer Res. 2013;3(1):21-33. Epub 2013 Jan 18.
During carcinogenesis, tumors induce dysfunctional development of hematopoietic cells. Myeloid lineage cells, in the form of myeloid derived suppressor cells (MDSCs) and alternatively polarized M2 macrophages, influence almost all types of cancers by regulating diverse facets of immunosuppression, angiogenesis, cell proliferation, growth and metastasis. One-third of Americans are obese, and accumulating evidence suggests that obesity is a risk factor for various cancers. However, the relationship between these immune players and obesity are not well-described. In this review, we evaluate potential mechanisms through which different aspects of obesity, namely insulin resistance, increased estrogen, adiposity and low grade chronic inflammation from adipose tissue macrophages, may coalesce to promote MDSC induction and M2 macrophage polarization, thereby facilitating cancer development. Detailed understanding of the interplay between obesity and myeloid mediated immunosuppression may provide novel avenues for therapeutic targeting, with the goal to reduce the challenge obesity presents towards gains made in cancer outcomes.
在致癌过程中，肿瘤诱导造血细胞功能失调的发展。髓系细胞以髓系来源的抑制细胞（MDSC）和选择性极化的 M2 巨噬细胞的形式存在，通过调节免疫抑制、血管生成、细胞增殖、生长和转移的各个方面来影响几乎所有类型的癌症。三分之一的美国人肥胖，越来越多的证据表明肥胖是各种癌症的危险因素。然而，这些免疫细胞与肥胖之间的关系还没有很好地描述。在这篇综述中，我们评估了不同方面的肥胖，即胰岛素抵抗、雌激素增加、脂肪组织巨噬细胞的肥胖和低度慢性炎症，可能通过何种机制共同促进 MDSC 的诱导和 M2 巨噬细胞的极化，从而促进癌症的发展。详细了解肥胖与骨髓介导的免疫抑制之间的相互作用可能为治疗靶点提供新的途径，目标是减少肥胖对癌症治疗结果的影响。
