Importance of MUC1 in the mechanism of resistance for anti-PD-1 inhibitor
| Project/Area Number |
20K17182
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 53030:Respiratory medicine-related
|
|---|
| Research Institution | Hiroshima University |
|---|
Principal Investigator |
NAMBA MASASHI 広島大学, 病院(医), 助教 (40848090)
|
|---|
| Project Period (FY) |
2020-04-01 – 2023-03-31
|
| Project Status |
Completed (Fiscal Year 2022)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | MUC1 / KL-6 / PD-L1 / PD-1 antibody / 肺癌 / 免疫チェックポイント阻害薬 |
|---|
| Outline of Research at the Start |
本研究は、免疫チェックポイント阻害薬に対する耐性機序にMUC1（KL-6）が関わっているのではないかと仮説を立て、計画されたものである。新規に樹立させた肺癌細胞株におけるMUC1とPD-L1の発現状況を評価しつつ、MUC1の発現の増減によって、PD-1阻害薬に対する感受性が変化するかどうかを探索する。本研究によって、MUC1がPD-1阻害薬の耐性化に関わっていることが明らかとなると、PD-1阻害薬の治療効果を予測するバイオマーカーとなることや、MUC1を治療標的とすることによってPD-1阻害薬の耐性を克服することが可能となることが期待される。
|
| Outline of Final Research Achievements |
Although there was a correlation between serum KL-6 and the therapeutic effect of the PD-1 antibody in patients with lung cancer, no correlation was found between the KL-6 values and the level of PD-L1 expression. Moreover, data from the immunohistochemical staining of KL-6 did not show a correlation with the therapeutic effect.
We used flow cytometry to evaluate whether there would be any changes in PD-L1 expression when KL-6 expression was knocked down with siRNA in lung cancer cell lines, but we were unable to confirm any clear changes. However, it should not be concluded that there is no relationship between KL-6 and PD-L1 based solely on the results of the flow cytometry. It is considered necessary to conduct additional experiments in the future.
|
| Academic Significance and Societal Importance of the Research Achievements |
免疫チェックポイント阻害薬が効かない肺癌患者の中に血清KL-6が高値のものがいることがわかっており、KL-6が治療標的となりえるかどうかを探索する研究である。PD-L1発現との関連に着目して研究を行ったが、現状ではその関与を明らかにすることはできなかった。
|
Report
(4 results)
Research Products
(10 results)
-
-
[Journal Article] 腹壁に進展発生した原発不明癌の1例2022
Author(s)
東野 諒, 難波 将史, 徳毛 健太郎, 森 馨一, 利田 明日香, 山内 理海, 岡本 渉, 檜井 孝夫, 有廣 光司, 杉山 一彦
-
Journal Title
広島医学
Volume: 75
Pages: 348-352
Related Report
Peer Reviewed / Open Access
-
-
-
-
[Journal Article] Extent of pulmonary fibrosis on high-resolution computed tomography is a prognostic factor in patients with pleuroparenchymal fibroelastosis.2020
Author(s)
Namba M, Masuda T, Takao S, Terada H, Yamaguchi K, Sakamoto S, Horimasu Y, Miyamoto S, Nakashima T, Iwamoto H, Ohshimo S, Fujitaka K, Hamada H, Awai K, Hattori N.
-
Journal Title
Respir Investig.
Volume: 58
Issue: 6
Pages: 465-472
DOI
Related Report
Peer Reviewed
-
-
-
[Presentation] Current status and future challenges of lung cancer genome medicine at our hospital2021
Author(s)
M Namba, K Tokumo, M Yamauchi, H Nakahara, Y Urabe, C. Nelson Hayes, Y Teratani, R Kobayashi, R Itamura, M Motonaga, K Yamaguchi, S Sakamoto, T Masuda, K Fujitaka, W Okamoto, K Arihiro, E Hiyama, N Hattori, T Hinoi, K Sugiyama
Organizer
The 25th Congress of the Asian Pacific Society of Respirology
Related Report
Int'l Joint Research
-
