Hormone receptor–positive breast cancer (HR+) is immunologically cold and has not benefited from advances in immunotherapy. In contrast, subsets of triple-negative breast cancer (TNBC) display high leukocytic infiltration and respond to checkpoint blockade. CD8⁺ T cells, the main effectors of anticancer responses, recognize MHC I–associated peptides (MAPs). Our work aimed to characterize the repertoire of MAPs presented by HR+ and TNBC tumors. Using mass spectrometry, we identified 57,094 unique MAPs in 26 primary breast cancer samples. MAP source genes highly overlapped between both subtypes. We identified 25 tumor-specific antigens (TSAs) mainly deriving from aberrantly expressed regions. TSAs were most frequently identified in TNBC samples and were more shared among The Cancer Genome Atlas (TCGA) database TNBC than HR+ samples. In the TNBC cohort, the predicted number of TSAs positively correlated with leukocytic infiltration and overall survival, supporting their immunogenicity in vivo. We detected 49 tumor-associated antigens (TAAs), some of which derived from cancer-associated fibroblasts. Functional expansion of specific T cell assays confirmed the in vitro immunogenicity of several TSAs and TAAs. Our study identified attractive targets for cancer immunotherapy in both breast cancer subtypes. The higher prevalence of TSAs in TNBC tumors provides a rationale for their responsiveness to checkpoint blockade.

中文翻译：

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乳腺癌免疫肽组含有许多共享的肿瘤抗原

激素受体阳性乳腺癌（HR+）在免疫学上是冷的，并且没有从免疫疗法的进步中受益。相比之下，三阴性乳腺癌 (TNBC) 的亚型表现出高白细胞浸润并对检查点封锁有反应。CD8 ⁺ T 细胞是抗癌反应的主要效应细胞，可识别 MHC I 相关肽 (MAP)。我们的工作旨在描述 HR+ 和 TNBC 肿瘤呈现的 MAP 的全部特征。使用质谱分析法，我们在 26 个原发性乳腺癌样本中鉴定出了 57,094 个独特的 MAP。MAP 源基因在两个亚型之间高度重叠。我们鉴定了 25 种肿瘤特异性抗原 (TSA)，主要源自异常表达区域。TSA 在 TNBC 样本中最常被识别，并且在癌症基因组图谱 (TCGA) 数据库 TNBC 中比 HR+ 样本更常见。在 TNBC 队列中，预测的 TSA 数量与白细胞浸润和总生存率呈正相关，支持其体内免疫原性。我们检测到 49 种肿瘤相关抗原 (TAA)，其中一些源自癌症相关成纤维细胞。特定 T 细胞测定的功能扩展证实了几种 TSA 和 TAA 的体外免疫原性。我们的研究确定了两种乳腺癌亚型的癌症免疫治疗的有吸引力的靶点。TNBC 肿瘤中 TSA 的较高患病率为其对检查点封锁的反应提供了依据。