Cancer Research @ UCC, University College Cork, Fourth Floor, Western Gateway Building, Western Road, Cork, Ireland.
School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland.
Cancer Immunol Immunother. 2019 Sep;68(9):1455-1465. doi: 10.1007/s00262-019-02381-1. Epub 2019 Aug 23.
Macrophages have been shown to infiltrate a wide range of malignancies and are often considered to promote tumour survival, growth and spread. However, the source and behaviour of discrete tumour-associated macrophage populations are still poorly understood. Here we show a novel method for the rational development of bone marrow-derived monocytes appropriate for the study of processes which involve the contribution of circulating inflammatory monocytes. We have shown that in response to tumour-conditioned medium, these cells upregulate CD206 and CD115, markers traditionally associated with M2-type macrophages. Treated cells show reduced capacity for cytokine secretion but significantly impact CD4 and CD8 T-cell proliferation and polarization. Coculture with conditioned bone marrow-derived monocytes significantly reduced CD4 T-cell proliferation but increased CD8 T-cell proliferation and granzyme B expression with significant induction of IFNγ secretion by both CD4 and CD8 T cells, indicating that these cells may have a role in promoting anti-cancer immunity.
巨噬细胞已被证明能浸润广泛的恶性肿瘤，通常被认为能促进肿瘤的存活、生长和扩散。然而，离散的肿瘤相关巨噬细胞群体的来源和行为仍知之甚少。在这里，我们展示了一种新的方法，可以合理地开发适合研究涉及循环炎症性单核细胞贡献的过程的骨髓来源的单核细胞。我们已经表明，这些细胞在响应肿瘤条件培养基时上调 CD206 和 CD115，这是与 M2 型巨噬细胞相关的传统标志物。经处理的细胞细胞因子分泌能力降低，但显著影响 CD4 和 CD8 T 细胞的增殖和极化。与条件培养基来源的单核细胞共培养显著降低了 CD4 T 细胞的增殖，但增加了 CD8 T 细胞的增殖和颗粒酶 B 的表达，同时显著诱导 CD4 和 CD8 T 细胞分泌 IFNγ，表明这些细胞可能在促进抗肿瘤免疫方面发挥作用。
