| Project/Area Number |
18K15612
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 52040:Radiological sciences-related
|
|---|
| Research Institution | National Cancer Center Japan |
|---|
Principal Investigator |
Hojo Hidehiro 国立研究開発法人国立がん研究センター, 東病院, 医員 (60638774)
|
|---|
| Project Period (FY) |
2018-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
|---|
| Keywords | 粒子線治療 / 免疫応答 / トランスクリプトーム / 食道癌 / 陽子線 / 重粒子線 / 炭素線 / 食道癌細胞 / トランスクリプトーム解析 / 陽子線治療 |
|---|
| Outline of Final Research Achievements |
We aimed to compare the immune responses after irradiation (IR) with X-ray, protons, and carbon ions in an oesophageal cancer cell line and the underlying mechanisms. An oesophageal cancer cell line, KYSE450, was irradiated with 1 fraction/15 GyE (Gy equivalent) of X-ray, proton, or carbon-ion beams, and then, the cells were harvested for RNA sequencing and gene enrichment analysis. We also knocked out STING and STAT1 in the quest for mechanistic insights. RNA sequencing data revealed that gene expression signatures and biological processes were different in KYSE450 irradiated with X-ray, proton, and carbon-ion beams 24 h after IR. However, after 3 days, a common gene expression signature was detected, associated with biological pathways involved in innate immune responses. Gene knock-out experiments revealed that the STING-STAT1 axis underlies the immune reactions after IR. X-Ray, proton, and carbon-ion IRs induced similar immune responses, regulated by the STING-STAT1 axis.
|
| Academic Significance and Societal Importance of the Research Achievements |
がん治療において、陽子線治療や炭素線治療は治療の選択肢の一つとして一般化されつつある。また、免疫チェックポイント阻害剤は放射線治療の増感剤として使用されているが、陽子線、炭素線照射後の免疫応答やそのメカニズムについては不明な点が多い。そこで我々は、それぞれの線質での免疫応答を比較解析する目的で研究を行った。結果、照射後６位時間時点で変動する遺伝子や生物学的経路は3つの線種で異なっていたが、24時間後からその共通性が高くなり、免疫応答関連遺伝子の発現も類似していた。このことから、X線で併用される免疫療法と同様に、陽子線、重粒子線治療との併用でも効果をあげることが期待できると考える。
|
