HR乳腺癌中肿瘤特异性CD8 T细胞特征揭示了淋巴结转移患者抗肿瘤反应受损。
Tumor-specific CD8 T cell characterization in HR breast cancer reveals an impaired antitumoral response in patients with lymph node metastasis.
作者信息
Pinho Mariana Pereira, Antoun Elie, Sandhar Balraj, Shu Ting, Gao Fei, Yang Xiaobao, Bates Adam, Cerundolo Lucia, Hamid Megat H B A, Maldonado-Perez David, Teague Renuka, Warner Eve, Winter Lucinda, Alham Nasullah Khalid, Verrill Clare, Lord Simon R, Rostron Timothy, Clark Sally-Ann, Waugh Craig, Sopp Paul, Conlon Chris, Fernandes Ricardo A, Harris Adrian L, Peng Yanchun, Adwani Asha, Dong Tao
机构信息
Medical Research Council Translational Immune Discovery Unit (MRC TIDU), Weatherall Institute of Molecular Medicine (WIMM), University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
出版信息
Cell Rep Med. 2025 Aug 19;6(8):102252. doi: 10.1016/j.xcrm.2025.102252. Epub 2025 Jul 28.
Most breast cancers express the estrogen receptor (ER), but the immune response of hormone receptor-positive (HR) breast cancer remains poorly characterized. Here, dendritic cells loaded with tumor lysate are used to identify tumor-reactive CD8 T cells, which are detected in most HR breast cancer patients, especially those with early-stage tumors. When present, the circulating antitumor CD8 response contains cytotoxic T cells with diverse specificity and T cell receptor (TCR) repertoire. Additionally, patients with blood cancer-specific T cells have significantly more CD8 tumor-infiltrating lymphocytes (TILs). Moreover, tumor-reactive TCR sequences are detected in the tumor, but at a significantly lower proportion in patients with lymph node involvement. Our data suggest that HR breast cancer patients with lymph node metastasis lack tumor-specific CD8 T cells with capacity to infiltrate the tumor at significant levels. However, early-stage patients have a diverse antitumor CD8 response that could be harnessed to develop immunotherapeutic approaches for late-stage HR patients.
大多数乳腺癌表达雌激素受体（ER），但激素受体阳性（HR）乳腺癌的免疫反应仍未得到充分表征。在这里，负载肿瘤裂解物的树突状细胞被用于识别肿瘤反应性CD8 T细胞，在大多数HR乳腺癌患者中都能检测到这些细胞，尤其是那些患有早期肿瘤的患者。当存在时，循环中的抗肿瘤CD8反应包含具有不同特异性和T细胞受体（TCR）库的细胞毒性T细胞。此外，具有血液癌症特异性T细胞的患者有明显更多的CD8肿瘤浸润淋巴细胞（TILs）。而且，在肿瘤中检测到肿瘤反应性TCR序列，但在有淋巴结受累的患者中比例显著更低。我们的数据表明，有淋巴结转移的HR乳腺癌患者缺乏能够大量浸润肿瘤的肿瘤特异性CD8 T细胞。然而，早期患者有多样化的抗肿瘤CD8反应，可用于开发针对晚期HR患者的免疫治疗方法。
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