Breast Medical Oncology, Yale School of Medicine, Yale Cancer Center, 300 George St, Suite 120, Rm 133, New Haven, CT, 06520, USA.
University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Breast Cancer Res Treat. 2019 May;175(1):247-259. doi: 10.1007/s10549-019-05156-5. Epub 2019 Feb 6.
African-American (AA) patients with triple-negative breast cancer (TNBC) are less likely to achieve pathologic complete response from neoadjuvant chemotherapy and have poorer prognosis than Caucasian patients with TNBC, suggesting potential biological differences by race. Immune infiltration is the most consistent predictive marker for chemotherapy response and improved prognosis in TNBC. In this study, we test the hypothesis that the immune microenvironment differs between AA and Caucasian patients.
RNA-seq expression data were obtained from The Cancer Genome Atlas (TCGA) database for 162 AA and 697 Caucasian breast cancers. Estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-positive, and TNBC subtypes were included in the analyses. Tumor infiltrating lymphocyte (TIL) counts, immunomodulatory scores, and molecular subtypes were obtained from prior publications for a subset of the TNBC cases. Differences in immune cell distributions and immune functions, measured through gene expression and TIL counts, as well as neoantigen, somatic mutation, amplification, and deletion loads, were compared by race and tumor subtype.
Immune metagene analysis demonstrated marginal immune attenuation in AA TNBC relative to Caucasian TNBC that did not reach statistical significance. The distributions of immune cell populations, lymphocyte infiltration, molecular subtypes, and genomic aberrations between AA and Caucasian subtypes were also not significantly different. The MHC1 metagene demonstrated increased expression in AA ER-positive cancers relative to Caucasian ER-positive cancers.
This study suggests that the immunological differences between AA and Caucasian breast cancers represented by TCGA data are subtle, if they exist at all. We observed no consistent racial differences in immune gene expression or TIL counts in TNBC by race. However, this study cannot rule out small differences in immune cell subtype distribution and activity status that may not be apparent in bulk RNA analysis.
非裔美国（AA）患者的三阴性乳腺癌（TNBC）患者接受新辅助化疗后获得病理完全缓解的可能性低于白种人 TNBC 患者，且预后较差，这表明种族间存在潜在的生物学差异。免疫浸润是预测 TNBC 患者化疗反应和改善预后的最一致的标志物。在这项研究中，我们检验了一个假设，即 AA 和白种人患者的免疫微环境存在差异。
从癌症基因组图谱（TCGA）数据库中获得了 162 例 AA 和 697 例白种人乳腺癌的 RNA-seq 表达数据。纳入分析的有雌激素受体（ER）阳性、人表皮生长因子受体 2（HER2）阳性和 TNBC 亚型。从部分 TNBC 病例的先前出版物中获得了肿瘤浸润淋巴细胞（TIL）计数、免疫调节评分和分子亚型。通过种族和肿瘤亚型比较了基因表达和 TIL 计数以及新抗原、体细胞突变、扩增和缺失负荷所衡量的免疫细胞分布和免疫功能的差异。
免疫元基因分析显示，AA TNBC 相对于白种人 TNBC 的免疫衰减程度存在边缘差异，但未达到统计学意义。AA 和白种人亚型之间的免疫细胞群分布、淋巴细胞浸润、分子亚型和基因组异常也没有显著差异。MHC1 元基因在 AA ER 阳性癌症中的表达高于白种人 ER 阳性癌症。
本研究表明，TCGA 数据所代表的 AA 和白种人乳腺癌之间的免疫学差异如果存在的话也是微小的。我们没有观察到 TNBC 按种族划分的免疫基因表达或 TIL 计数存在一致的种族差异。然而，本研究不能排除免疫细胞亚型分布和活性状态的微小差异，这些差异在批量 RNA 分析中可能不明显。
