Immune Checkpoint Profiles in Luminal B Breast Cancer (Alliance)
Immune Checkpoint Profiles in Luminal B Breast Cancer (Alliance)
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DOI：
10.1093/jnci/djz213
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发表时间：
2020-07-01
影响因子：
10.3
通讯作者：
Ellis, Matthew J.
中科院分区：
文献类型：
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作者：
Anurag, Meenakshi;Zhu, Mayanne;Ellis, Matthew J.
背景：与雌激素受体(ER)阴性的乳腺癌不同，ER阳性乳腺癌的预后受淋巴细胞含量的影响较小，这表明存在可能针对该疾病亚群的免疫耐受机制。方法：对来自ACOSOG Z1031(Alliance)新辅助芳香酶抑制物(AI)试验的微阵列数据的监督分析发现，在腔(Lum)B乳腺癌中，与AI敏感的Lumb乳腺癌(33例Ki67>；0.4)(33例Ki67>；AI；人工智能10%)。使用WebGestalt进行过度表征分析。结果：30个候选基因与抗AI增殖呈正相关(r>；=0.4)，上调幅度超过2倍。基因本体论表明，靶向免疫检查点(IC)组分IDO1、LAG3和PD1是过度表达的候选抗性基因(P
Background: Unlike estrogen receptor (ER)-negative breast cancer, ER-positive breast cancer outcome is less influenced by lymphocyte content, indicating the presence of immune tolerance mechanisms that may be specific to this disease subset.Methods: A supervised analysis of microarray data from the ACOSOG Z1031 (Alliance) neoadjuvant aromatase inhibitor (AI) trial identified upregulated genes in Luminal (Lum) B breast cancers that correlated with AI-resistant tumor proliferation (percentage of Ki67-positive cancer nuclei, Pearson r > 0.4) (33 cases Ki67 > 10% on AI) vs LumB breast cancers that were more AI sensitive (33 cases Ki67 < 10% on AI). Overrepresentation analysis was performed using WebGestalt. All statistical tests were two-sided.Results: Thirty candidate genes positively correlated (r >= 0.4) with AI-resistant proliferation in LumB and were upregulated greater than twofold. Gene ontologies identified that the targetable immune checkpoint (IC) components IDO1, LAG3, and PD1 were overrepresented resistance candidates (P