Different Lipid Regulation in Ovarian Cancer: Inhibition of the Immune System

被引:20
|
作者
Wefers, Christina [1 ,2 ]
Duiveman-de Boer, Tjitske [1 ]
Zusterzeel, Petra L. M. [2 ]
Massuger, Leon F. A. G. [2 ]
Fuchs, David [3 ]
Torensma, Ruurd [1 ]
Wheelock, Craig E. [3 ]
de Vries, I. Jolanda M. [1 ]
机构
[1] Radboudumc, Radboud Inst Mol Life Sci, Dept Tumor Immunol, Geert Grootepl Zuid 28, NL-6525 GA Nijmegen, Netherlands
[2] Radboudumc, Dept Obstet & Gynecol, Geert Grootepl 10, NL-6525 GA Nijmegen, Netherlands
[3] Karolinska Inst, Div Physiol Chem 2, Dept Med Biochem & Biophys, Scheeles Vag 2, SE-17177 Stockholm, Sweden
基金
瑞典研究理事会;
关键词
lipid intermediates; paralyzed T cells; modified lipid metabolism; tumor microenvironment; FATTY-ACID CATABOLISM; PPAR-GAMMA AGONISTS; 9-HYDROXYOCTADECADIENOIC ACID; CELL-CYCLE; T-CELLS; MEDIATORS; IL-2; PROLIFERATION; MICROENVIRONMENT; ASSOCIATION;
D O I
10.3390/ijms19010273
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Lipid metabolism is altered in several cancer settings leading to different ratios of intermediates. Ovarian cancer is the most lethal gynecological malignancy. Cancer cells disperse in the abdominal space and ascites occurs. T cells obtained from ascites are unable to proliferate after an antigenic stimulus. The proliferation of ascites-derived T cells can be restored after culturing the cells for ten days in normal culture medium. No pathway aberrancies were detected. The acellular fraction of ascites can inhibit the proliferation of autologous as well as allogeneic peripheral blood lymphocytes, indicating the presence of soluble factors that interfere with T cell functionality. Therefore, we analyzed 109 lipid mediators and found differentially regulated lipids in suppressive ascitic fluid compared to normal abdominal fluid. Our study indicates the presence of lipid intermediates in ascites of ovarian cancer patients, which coincidences with T cell dysfunctionality. Since the immune system in the abdominal cavity is compromised, this may explain the high seeding efficiency of disseminated tumor cells. Further research is needed to fully understand the correlation between the various lipids and T cell proliferation, which could lead to new treatment options.
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页数:16
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