2016 Fiscal Year Final Research Report
Immune-mediated mechanisms of resistance to molecular targeting therapy against NSCLC
| Project/Area Number |
26290050
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Partial Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Tumor therapeutics
|
|---|
| Research Institution | Keio University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
菰原 義弘 熊本大学, その他の研究科, 准教授 (40449921)
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Keywords | 腫瘍免疫 / 肺腺癌 / ミエロイド細胞 / PD-1 / EGFR-TKI / 治療抵抗性 |
|---|
| Outline of Final Research Achievements |
As immune-mediated factors which are critical to reduce sensitibity and/or trigger resistance to EGF-TKI agains NSCLC through the analysis of novel spontaneous NSCLC models and clinical samples, we identified signaling pathways related to differentiation and activation of M2 macrophages and MDSC, two major immunosuppressive myeloid cells, as important factor to predict low sensitivity and emergence of resistant-associated mutation (T790M) to EGF-TKI against lung adenocarcinoma. Moreover, the combination of CSF1 inhibitors and EGF^TKI dramatically reduced incidence of spontaneous lung adenocarcinoma in mouse models. On the other hands, there are no involvement of immune checkpoint pathways as immune factors to regulate lung adenocarcinoma.It is important to clarify novel immune-mediated mechanisms other than immune checkpoint such as PD-1 to regulate responsiveness of EGFR-TKI against lung adenocarcinomas.
|
| Free Research Field |
腫瘍免疫
|
