Immunosuppressive parameters in serum of ovarian cancer patients change during the disease course
Immunosuppressive parameters in serum of ovarian cancer patients change during the disease course
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DOI：
10.1080/2162402x.2015.1111505
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发表时间：
2016-01-01
期刊：
影响因子：
7.2
通讯作者：
Vergote, Ignace
中科院分区：
文献类型：
--
作者：
Coosemans, An;Decoene, Judit;Vergote, Ignace
肿瘤细胞可以逃脱免疫控制，导致癌症生长。调节性T细胞（Treg）、髓源性抑制细胞（MDSC）和肿瘤相关巨噬细胞（TAM）在免疫逃逸中至关重要。TAM根据其免疫特性进行分类，M1是免疫刺激性的，而M2是免疫抑制性的。到目前为止，研究主要集中在这些细胞的肿瘤内行为。另一方面，本研究探讨了卵巢癌和输卵管癌患者疾病过程中与Treg、MDSC和TAM相关的关键代谢物[IL-4（白细胞介素）、IL-13、IL-10、VEGF-A（血管内皮生长因子）、CCL-2（趋化因子（C-C）基序配体2）和TGF-β（转化生长因子）]的全身变化。因此，在诊断时、（间隔）减瘤手术后和化疗（紫杉醇-卡铂）后分析血清样本。我们还确定了半乳糖凝集素-1（gal-1），参与血管生成和肿瘤介导的免疫逃避。我们发现化疗后IL-10、VEGF-A、TGF-β和β-D-半乳糖苷酶的水平显著低于诊断水平，而半乳糖苷1的水平则高于诊断水平。减积手术后，IL-10显著降低。Gal-1和CCL-2是无进展生存期和总生存期的独立预后因素（多因素分析）。这些结果将有助于我们在未来的治疗决策，以进一步调节免疫系统的积极方式。
Neoplastic cells can escape immune control leading to cancer growth. Regulatory T cells (Treg), myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) are crucial in immune escape. TAM are divided based on their immune profile, M1 are immunostimulatory while M2 are immunosuppressive. Research so far has mainly focused on the intratumoral behavior of these cells. This study, on the other hand, explored the systemic changes of the key metabolites [IL-4 (interleukin), IL-13, arginase, IL-10, VEGF-A (vascular endothelial growth factor), CCL-2 (chemokine (C-C) motif ligand 2) and TGF- (transforming growth factor)] linked to Treg, MDSC and TAM during the course of the disease in ovarian and fallopian tube cancer patients. Serum samples were therefore analyzed at diagnosis, after (interval)-debulking surgery and after chemotherapy (paclitaxel-carboplatin). We also determined galectin-1 (gal-1), involved in angiogenesis and tumor-mediated immune evasion. We found significantly lower levels of IL-10, VEGF-A, TGF- and arginase and higher levels of gal-1 after chemotherapy compared to diagnosis. After debulking surgery, a decrease in IL-10 was significant. Gal-1 and CCL-2 appeared independent prognostic factors for progression-free and overall survival (OS) (multivariate analysis). These results will help us in the decision making of future therapies in order to further modulate the immune system in a positive way.