Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
Cancer Commun (Lond). 2023 Jun;43(6):661-684. doi: 10.1002/cac2.12429. Epub 2023 May 9.
Characterizing the unique immune microenvironment of each tumor is of great importance for better predicting prognosis and guiding cancer immunotherapy. However, the unique features of the immune microenvironment of triple negative breast cancer (TNBC) compared with other subtypes of breast cancer remain elusive. Therefore, we aimed to depict and compare the immune landscape among TNBC, human epidermal growth factor receptor 2-positive (HER2 ) breast cancer, and luminal-like breast cancer.
Single-cell RNA sequencing (scRNA-seq) was performed on CD45 immune cells isolated from human normal breast tissues and primary breast tumors of various subtypes. By analyzing the scRNA-seq data, immune cell clusters were identified and their proportions as well as transcriptome features were compared among TNBC, human HER2 breast cancer, and luminal-like breast cancer. Pseudotime and cell-cell communication analyses were also conducted to characterize the immune microenvironment.
ScRNA-seq data of 117,958 immune cells were obtained and 31 immune clusters were identified. A unique immunosuppressive microenvironment in TNBC was decoded as compared to that in HER2 or luminal-like breast cancer, which was characterized by higher proportions of regulatory T cells (Tregs) and exhausted CD8 T cells and accompanied by more abundant plasma cells. Tregs and exhausted CD8 T cells in TNBC exhibited increased immunosuppression signature and dysfunctional scores. Pseudotime analyses showed that B cells tended to differentiate to plasma cells in TNBC. Cell-cell communication analyses indicated that these unique features are fostered by the diversified T cell-B cell crosstalk in TNBC. Based on the T cell-B cell crosstalk, a prognostic signature was established that could effectively predict the prognosis status for patients with TNBC. Additionally, it was found that TNBC had a higher proportion of cytotoxic natural killer (NK) cells, whereas HER2 or luminal-like breast cancer lost this feature, suggesting that HER2 or luminal-like breast cancer, but not TNBC, may benefit from NK-based immunotherapy.
This study identified a distinct immune feature fostered by T cell-B cell crosstalk in TNBC, which provides better prognostic information and effective therapeutic targets for breast cancer.
对每个肿瘤独特的免疫微环境进行特征描述，对于更好地预测预后和指导癌症免疫治疗非常重要。然而，三阴性乳腺癌 (TNBC) 与其他乳腺癌亚型相比，其免疫微环境的独特特征仍难以捉摸。因此，我们旨在描绘和比较 TNBC、人表皮生长因子受体 2 阳性 (HER2) 乳腺癌和 luminal 样乳腺癌之间的免疫景观。
对来自人正常乳腺组织和各种亚型原发性乳腺癌的 CD45 免疫细胞进行单细胞 RNA 测序 (scRNA-seq)。通过分析 scRNA-seq 数据，鉴定免疫细胞簇，并比较 TNBC、HER2 乳腺癌和 luminal 样乳腺癌之间的比例及其转录组特征。还进行了伪时间和细胞间通信分析，以描绘免疫微环境。
获得了 117958 个免疫细胞的 scRNA-seq 数据，并鉴定了 31 个免疫簇。与 HER2 或 luminal 样乳腺癌相比，TNBC 中解码出独特的免疫抑制微环境，其特征是调节性 T 细胞 (Treg) 和耗竭的 CD8 T 细胞比例较高，并伴有更丰富的浆细胞。TNBC 中的 Treg 和耗竭的 CD8 T 细胞表现出增加的免疫抑制特征和功能障碍评分。伪时间分析表明，B 细胞在 TNBC 中倾向于分化为浆细胞。细胞间通信分析表明，这些独特的特征是由 TNBC 中多样化的 T 细胞-B 细胞相互作用促成的。基于 T 细胞-B 细胞相互作用，建立了一个预后签名，可以有效地预测 TNBC 患者的预后状态。此外，还发现 TNBC 具有更高比例的细胞毒性自然杀伤 (NK) 细胞，而 HER2 或 luminal 样乳腺癌则失去了这一特征，这表明 HER2 或 luminal 样乳腺癌，而不是 TNBC，可能受益于基于 NK 的免疫治疗。
本研究鉴定了 TNBC 中由 T 细胞-B 细胞相互作用促进的独特免疫特征，为乳腺癌提供了更好的预后信息和有效的治疗靶点。
