| Project/Area Number |
16K09596
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Respiratory organ internal medicine
|
|---|
| Research Institution | Kurume University |
|---|
Principal Investigator |
Koichi Azuma 久留米大学, 医学部, 講師 (00368896)
|
|---|
| Research Collaborator |
Matsuo Norikazu
Sasada Tetsuro
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 肺癌 / CXCL2 / PD-1阻害剤 / PD-L1 / 免疫療法 / バイオマーカー / 非小細胞肺癌 / 炎症性サイトカイン / EGFR / PD-1 / NSCLC / CD8 / ニボルマブ / EGFR遺伝子変異 / 免疫寛容 |
|---|
| Outline of Final Research Achievements |
Although programmed death (PD)-1 immune checkpoint therapies target the immune system, relationship between inflammatory factors and clinical outcome of anti-PD-1 therapy in non-small cell lung cancer (NSCLC) patients is not fully elucidated. Here we attempted to examine association between soluble immune mediators and treatment outcome of PD-1 inhibitors in patients with advanced/recurrent NSCLC receiving anti-PD-1 therapy. The change in the plasma CXCL2 level was also significantly associated with treatment-related AEs.In the validation cohort, however, only the changes in the plasma levels of CXCL2 and MMP2 after treatment were associated with PFS, and these changes were maintained during the course of anti-PD-1 therapy in the patients with better clinical outcomes.Since CXCL2 and MMP2 can be easily measured by minimally invasive blood sampling, they could be useful to predict and monitor clinical outcomes in NSCLC patients with PD-1 inhibitor therapy.
|
| Academic Significance and Societal Importance of the Research Achievements |
PD-1/PD-L1などの分子・経路を標的とした免疫チェックポイント阻害薬は各種がん患者に対して臨床応用されている。進行/再発非小細胞肺癌患者に対して抗PD-1抗体療法を実施した症例の末梢血を用いて88種の可溶性因子をマルチプレックスアッセイにて測定し、抗PD-1抗体療法の治療効果との関連を探索した。ケモカインの一種であるCXCL2の治療前と6週間後の変化値が奏効率と無増悪生存期間と関係していた抗PD-1抗体療法中の末梢血中CXCL2の動態を測定することにより抗PD-1抗体の治療効果をモニタリングできる可能性を見いだし,炎症性サイトカインが免疫逃避機構に関与する可能性も示した。
|
