Stanton Sasha, Schmitz Frank, Copeland Wilbert, DellAringa Justine, Newhall Kathryn, Disis Mary
Earle A. Chiles Research Institute.
Fred Hutchinson Cancer Research Institute.
Res Sq. 2024 Aug 2:rs.3.rs-4542494. doi: 10.21203/rs.3.rs-4542494/v1.
In breast cancer, triple negative (TN) breast cancer has most responses to immune checkpoint inhibitor (ICI) therapy. Lymphocyte infiltrate does not impact prognosis in Hormone receptor positive HER2 negative (HR + HER2-) breast tumors and few HR + HER2- tumors respond to ICI. We contrasted immune-associated gene expression between 119 TN and 475 HR + HER2- breast tumors from The Cancer Genome Atlas (TCGA) and confirmed our findings in 299 TN and 1369 HR + HER2- breast tumors in the METABRIC database. TN and HR+ HER2- tumors grouped into immune-high or -low tumors, both subtypes were represented in the immune-high group. The largest difference between the immune-high TN and HR + HER2- tumors was TN tumors had more abundant T and T CD4 T cells while HR + HER2- tumors had more abundant fibroblasts (logFC > 0.3; < 10×10). This suggests an immune-high signature is not dictated by breast cancer subtype, but fibroblast subsets associated with worse outcome were higher in the immune-high HR + HER2- tumors.
在乳腺癌中,三阴性(TN)乳腺癌对免疫检查点抑制剂(ICI)治疗的反应最为显著。淋巴细胞浸润对激素受体阳性人表皮生长因子受体2阴性(HR + HER2-)乳腺肿瘤的预后没有影响,并且很少有HR + HER2-肿瘤对ICI有反应。我们对比了来自癌症基因组图谱(TCGA)的119例TN乳腺肿瘤和475例HR + HER2-乳腺肿瘤之间的免疫相关基因表达,并在METABRIC数据库中的299例TN乳腺肿瘤和1369例HR + HER2-乳腺肿瘤中证实了我们的发现。TN和HR + HER2-肿瘤分为免疫高或低的肿瘤,两种亚型都出现在免疫高的组中。免疫高的TN肿瘤和HR + HER2-肿瘤之间最大的差异在于,TN肿瘤有更丰富的T细胞和CD4 + T细胞,而HR + HER2-肿瘤有更丰富的成纤维细胞(logFC> 0.3;P <10×10)。这表明免疫高特征并非由乳腺癌亚型决定,但是与较差预后相关的成纤维细胞亚群在免疫高的HR + HER2-肿瘤中比例更高。