The elucidation of the mechanisms of sensitivity and resistance to anti VEGF antibodies in ovarian cancer

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04309
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Kyoto University
• Principal Investigator: KOSHIYAMA MASAFUMI 京都大学, 医学研究科, 客員研究員 (50724390)
• Co-Investigator(Kenkyū-buntansha): 馬場 長 京都大学, 医学研究科, 准教授 (60508240) ; 濱西 潤三 京都大学, 医学研究科, 講師 (80378736) ; 小西 郁生 京都大学, 医学研究科, 名誉教授 (90192062) ; 松村 謙臣 京都大学, 医学研究科, 准教授 (20452336)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 抗VEGF抗体 / 感受性 / 耐性 / 免疫抑制 / 骨髄由来免疫抑制性細胞(MDSCs) / GM-CSF

Outline of Final Research Achievements

The elucidation of the mechanism underlying the development of resistance to anti-VEGF antibodies in ovarian cancer is urgently required. We found that immunosuppression in the tumor microenvironment is associated with resistance to anti-VEGF therapy with the use of preclinical models. Anti-VEGF therapy induced myeloid-derived suppressor cells (MDSCs), which suppressed lymphocyte activity. Anti-VEGF therapy induced tumor hypoxia, which up-regulated the GM-CSF expression in tumor cells and recruited MDSCs into the tumor site. The blockade of GM-CSF signaling improved tumor immunity and enhanced the efficacy of anti-VEGF therapy. Treatments targeting MDSCs induced by VEGF signaling may improve prognosis in patients with high-grade serous ovarian cancer. The development of therapies combining anti-VEGF therapy with drugs targeting tumor immunity is expected.

Free Research Field

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