| Project/Area Number |
16K11152
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Obstetrics and gynecology
|
|---|
| Research Institution | Saitama Medical University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
松下 博和 愛知県がんセンター(研究所), 腫瘍免疫制御TR分野, 分野長 (80597782)
織田 克利 東京大学, 医学部附属病院, 准教授 (30359608)
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | 卵巣明細胞癌 / 免疫 / ネオアンチゲン / T細胞 / 予後 / エクソーム / 癌 / 免疫学 / 卵巣 |
|---|
| Outline of Final Research Achievements |
A total of 74 cases of ovarian clear cell carcinoma (CCC) were analyzed in this study. Exome sequencing and expression array were performed. Mutations, neoantigen load, antigen presentation machinery and immune profile were investigated. The number of neoepitopes per mutation (neoantigen frequency, NF) was further analyzed. A correlation between high NF with decreased progression-free survival (PFS) was found. A cox multivariate regression analysis demonstrated that the high NF was an independent prognostic factor for PFS. Immune related genes were frequently highly expressed in tumors with low NF, suggesting evidence of immunoediting in the low NF group. In contrast, we observed decreased HLA class I expression as well as increased PD1/CD8 ratio in tumors with high NF. These results suggest that tumors with high NF in CCC might have received insufficient immunoediting due to an immunosuppressive tumor microenvironment.
|
| Academic Significance and Societal Importance of the Research Achievements |
卵巣明細胞癌74例のエクソームシーケンスデータを元に、腫瘍変異遺伝子情報からMHC class I 結合エピトープの予測を行ない、免疫編集に関して検討した。免疫編集とは腫瘍の発生、発育の段階で抗腫瘍免疫が働いた場合、ネオアンチゲンを持ったクローンが排除されるため、腫瘍の変異遺伝子数に比較してネオアンチゲンの数が減少する可能性が考えられている。そこで卵巣明細胞癌で免疫編集が起こっているかを確認するために、ネオアンチゲン数を変異遺伝子数で割ったものを免疫編集の指標（neoantigen frequency, NF）として検討した
|
