Abstract A090: The Duffy Antigen Receptor for Chemokines (DARC) influences levels of tumor-associated leukocytes in the breast tumor microenvironment

Rachel N. Martini, Brittany D. Jenkins, C. Yates, L. Newman, M. Davis
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Abstract

The regulation of immune cell infiltration into the tumor microenvironment can influence disease prognosis. The specific populations that are present can inform potential treatment options. This work investigates immune cell regulation in the breast cancer tumor microenvironment, specifically how an atypical chemokine receptor, known as the Duffy Antigen Receptor for Chemokines (DARC/ACKR1) can influence levels of leukocyte populations in the breast tumor environment. DARC is a nonsignaling receptor able to bind both the CC and CXC classes of chemokines, and mainly functions to modulate levels of chemokines in circulation, and aid in chemokine transport in tissues. In this regard, DARC expression may determine the profile of immune response.To investigate DARC expression and its effects on tumor-associated leukocyte (TAL) populations, we obtained RNA-seq data from The Cancer Genome Atlas (TCGA) Breast Cancer cohort. We proceeded through our analysis with those samples denoted as primary tumor samples (n=400). To estimate the relative abundance of TAL populations, we used the CIBERSORT online platform, which estimates fractions of 22 different TAL populations based on gene expression data. After completing the CIBERSORT analysis, we proceeded with only those samples that had a significant CIBERSORT output (n=167). In our analysis, we found that the total abundance of all TALs was significantly higher in tumors that have high DARC expression (p Citation Format: Rachel Martini, Brittany D. Jenkins, Clayton Yates, Lisa Newman, Melissa Davis. The Duffy Antigen Receptor for Chemokines (DARC) influences levels of tumor-associated leukocytes in the breast tumor microenvironment [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A090.
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Duffy抗原趋化因子受体(DARC)影响乳腺肿瘤微环境中肿瘤相关白细胞的水平
免疫细胞对肿瘤微环境浸润的调控影响疾病预后。现有的特定人群可以为潜在的治疗方案提供信息。这项工作研究了乳腺癌肿瘤微环境中的免疫细胞调节,特别是一种非典型趋化因子受体,即达菲趋化因子抗原受体(DARC/ACKR1)如何影响乳腺癌肿瘤环境中白细胞群的水平。DARC是一种非信号受体,能够结合CC和CXC类趋化因子,主要作用是调节循环中趋化因子的水平,并帮助趋化因子在组织中的运输。在这方面,DARC的表达可能决定了免疫反应的概况。为了研究DARC表达及其对肿瘤相关白细胞(TAL)群体的影响,我们从癌症基因组图谱(TCGA)乳腺癌队列中获得了RNA-seq数据。我们继续对原发肿瘤样本(n=400)进行分析。为了估计TAL种群的相对丰度,我们使用了CIBERSORT在线平台,该平台基于基因表达数据估计了22个不同TAL种群的部分。在完成CIBERSORT分析之后,我们只处理那些具有显著CIBERSORT输出的样本(n=167)。在我们的分析中,我们发现在具有高DARC表达的肿瘤中,所有tal的总丰度明显更高(p引文格式:Rachel Martini, Brittany D. Jenkins, Clayton Yates, Lisa Newman, Melissa Davis)。达菲抗原趋化因子受体(DARC)影响乳腺肿瘤微环境中肿瘤相关白细胞的水平[摘要]。第四届CRI-CIMT-EATI-AACR国际癌症免疫治疗会议:将科学转化为生存;2018年9月30日至10月3日;纽约,纽约。费城(PA): AACR;癌症免疫学杂志2019;7(2增刊):摘要nr A090。
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