Systematic analysis of cellular signaling involved in the melanoma induced immunosuppression

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670506
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Keio University
• Principal Investigator: KAWAKAMI Yutaka 慶應義塾大学, 医学部, 教授 (50161287)
• Co-Investigator(Kenkyū-buntansha): TSUKAMOTO Nobuo 慶應義塾大学, 医学部, 助教 (20407117) ; YAGUCHI Tomonori 慶應義塾大学, 医学部, 助教 (40424163)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 悪性黒色腫 / がん免疫療法 / 免疫抑制 / 網羅的分子解析 / 分子標的治療薬

Outline of Final Research Achievements

Immunotherapy is now known to be effective on melanoma, but not all the patients. One of the reasons is immunosuppression caused by melanoma cells. Understanding it's mechanism may lead to improvement of melanoma treatment. In this study, by systematic screening of molecules involved in the human melanoma induced immunosuppression using low molecular weight compound libraries and siRNA libraries, we found that TGF-β and MAPK signaling pathways are important for the human melanoma induced immunosuppression in both induction and effector phases of anti-melanoma specific T-cells. We identified cellular and molecular mechanisms in the TGF-β and MAPK induced immunosuppression. These results indicate that blockade of TGF-β or MAPK pathway may be useful for the improvement of current melanoma therapies, particularly for cancer immunotherapy.

Free Research Field

腫瘍免疫学