2017 Fiscal Year Final Research Report
Resistance mechanis of molecular targeted therapy and tumor micro environment as the immune-checkpoint inhibitor's biomarker
| Project/Area Number |
16K21506
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor diagnostics
Medical genome science
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| Research Institution | Kindai University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | バイオマーカー / 個別化医療 / 免疫チェックポイント阻害薬 |
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| Outline of Final Research Achievements |
The efficacy of PD-1 blockade in EGFR mutated NSCLC with different mechanisms of acquired resistance to EGFR-TKIs is unknown. We retrospectively evaluated nivolumab efficacy and immune-related factors in such patients according to their status for the T790M resistance mutation of EGFR.We identified 25 patients with EGFR mutation-positive NSCLC who were treated with nivolumab. Whole-exome sequencing of tumor DNA was carried out to identify gene alterations.
Efficacy of nivolumab tended to increase as the PD-L1 expression level increased with cutoff values of 10% and 50%.The proportion of tumors with a PD-L1 level of10% or50% was higher among T790M-negative patients than among -positive patients. Nivolumab responders had a significantly higher CD8+ TIL density and nonsynonymous mutation burden.
T790M-negative patients with EGFR mutation-positive NSCLC are more likely to benefit from nivolumab after EGFR-TKI treatment, possibly as a result of a higher PD-L1 expression level.
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| Free Research Field |
臨床腫瘍学
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