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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 530 - 542 (13page)
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Purpose Combination of radiotherapy and immune checkpoint blockade such as programmed death- 1 (PD-1) or programmed death-ligand 1 (PD-L1) blockade is being actively tested in clinical trial. We aimed to identify a subset of patients that could potentially benefit from this strategy using The Cancer Genome Atlas (TCGA) dataset for glioblastoma (GBM). Materials and Methods A total of 399 cases were clustered into radiosensitive versus radioresistant (RR) groups based on a radiosensitivity gene signature and were also stratified as PD-L1 high versus PD-L1 low groups by expression of CD274 mRNA. Differential and integrated analyses with expression and methylation data were performed. CIBERSORT was used to enumerate the immune repertoire that resulted from transcriptome profiles. Results We identified a subset of GBM, PD-L1-high-RR group which showed worse survival compared to others. In PD-L1-high-RR, differentially expressed genes (DEG) were highly enriched for immune response and mapped into activation of phosphoinositide 3-kinase–AKT and mitogen-activated protein kinase (MAPK) signaling pathways. Integration of DEG and differentially methylated region identified that the kinase MAP3K8-involved in T-cell receptor signaling was upregulated and BAI1, a factor which inhibits angiogenesis, was silenced. CIBERSORT showed that a higher infiltration of the immune repertoire, which included M2 macrophages and regulatory T cells. Conclusion Taken together, PD-L1-high-RR group could potentially benefit from radiotherapy combined with PD-1/PD-L1 blockade and angiogenesis inhibition.
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참고문헌 (30)
참고문헌 신청
Ostrom QT / 2016 / CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009-2013 / Neuro Oncol. 18(Suppl 5):v1~v75
Crane CA / 2012 / Soluble factors secreted by glioblastoma cell lines facilitate recruitment, survival, and expansion of regulatory T cells : implications for immunotherapy / Neuro Oncol 14:584~595
Huang Y / 2013 / Vascular normalization as an emerging strategy to enhance cancer immunotherapy / Cancer Res 73:2943~2948
Nduom EK / 2016 / PD-L1 expression and prognostic impact in glioblastoma / Neuro Oncol 18:195~205
Topalian SL / 2012 / Safety, activity, and immune correlates of anti-PD-1 antibody in cancer / N Engl J Med 366:2443~2454
Crane CA / 2012 / Soluble factors secreted by glioblastoma cell lines facilitate recruitment, survival, and expansion of regulatory T cells : implications for immunotherapy / Neuro Oncol 14:584~595
Huang Y / 2013 / Vascular normalization as an emerging strategy to enhance cancer immunotherapy / Cancer Res 73:2943~2948
Nduom EK / 2016 / PD-L1 expression and prognostic impact in glioblastoma / Neuro Oncol 18:195~205
Topalian SL / 2012 / Safety, activity, and immune correlates of anti-PD-1 antibody in cancer / N Engl J Med 366:2443~2454
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