Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response
Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response
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DOI：
10.4049/jimmunol.179.2.977
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发表时间：
2007-07-15
影响因子：
4.4
通讯作者：
Ostrand-Rosenberg, Suzanne
中科院分区：
文献类型：
--
作者：
Sinha, Pratima;Clements, Virginia K.;Ostrand-Rosenberg, Suzanne
虽然免疫系统有可能防止恶性肿瘤，但许多癌症患者的免疫抑制。髓源性抑制细胞（MDSC）在许多肿瘤患者和动物中升高，并通过阻断CD 4（+）和CD 8（+）T细胞活化而促进免疫抑制。使用自发转移的4 T1小鼠乳腺癌，我们现在证明MDSC和巨噬细胞之间的串扰通过增加MDSC产生IL-10和减少巨噬细胞产生IL-12来进一步破坏肿瘤免疫。MDSC和巨噬细胞之间的串扰需要细胞-细胞接触，并且IL-12的减少依赖于MDSC产生IL-10。使用化疗药物吉西他滨（可减少MDSC）治疗，通过允许T细胞活化、维持巨噬细胞产生IL-12和防止IL-10产生增加，促进产生M1巨噬细胞的IL-4 R α（-/-）小鼠中已建立的转移性疾病的排斥反应。因此，MDSC通过抑制T细胞活化和通过与巨噬细胞相互作用以增加IL-10和减少IL-12产生来损害肿瘤免疫，从而促进肿瘤促进2型应答，这一过程可以被吉西他滨部分逆转。
Although the immune system has the potential to protect against malignancies, many individuals with cancer are immunosuppressed. Myeloid-derived suppressor cells (MDSC) are elevated in many patients and animals with tumors, and contribute to immune suppression by blocking CD4(+) and CD8(+) T cell activation. Using the spontaneously metastatic 4T1 mouse mammary carcinoma, we now demonstrate that cross-talk between MDSC and macrophages further subverts tumor immunity by increasing MDSC production of IL-10, and by decreasing macrophage production of IL-12. Cross-talk between MDSC and macrophages requires cell-cell contact, and the IL-12 decrease is dependent on MDSC production of IL-10. Treatment with the chemotherapeutic drug gemcitabine, which reduces MDSC, promotes rejection of established metastatic disease in IL-4R alpha(-/-) mice that produce M1 macrophages by allowing T cell activation, by maintaining macrophage production of IL-12, and by preventing increased production of IL-10. Therefore, MDSC impair tumor immunity by suppressing T cell activation and by interacting with macrophages to increase IL-10 and decrease IL-12 production, thereby promoting a tumor-promoting type 2 response, a process that can be partially reversed by gemcitabine.