免疫检查点抑制剂 (ICIs) 已被引入乳腺癌 (BC) 治疗中，需要更好的生物标志物来预测疗效。循环肿瘤细胞 (CTC) 在 BC 中具有预后作用，但在 ICI 治疗背景下对 CTC 的了解有限。在这项研究中，对参加两项调查 ICI 加化疗的随机试验的 82 名转移性 BC 患者进行了 CTC（CellSearch 系统）的连续采样评估。还测量了 CTC 上的程序性死亡配体 1 (PD-L1) 表达。基线时每 7.5mL ≥2 个 CTC 的患者肿瘤中的基因表达谱表明 T 细胞活性增加，包括三阴性 (P = 0.010) 和激素受体阳性 (P = 0.024) 疾病。 Luminal A BC 患者的 CTC 水平较高。 CTC 状态和结果之间的关联在治疗 4 周后最为明显。在 6/17 CTC 阳性患者中观察到 CTC 中的 PD-L1 表达，并且与较差的生存率相关。总之，我们的研究表明 CTC 数量可能会影响肿瘤的免疫组成以及预后。这些发现表明，在接受免疫疗法治疗的 BC 患者中，有可能使用 CTC 作为可获取的生物标志物来源。© 2024 作者。约翰·威利出版的《分子肿瘤学》

Immune checkpoint inhibitors (ICIs) have been introduced in breast cancer (BC) treatment and better biomarkers are needed to predict benefit. Circulating tumor cells (CTCs) are prognostic in BC, but knowledge is limited on CTCs in the context of ICI therapy. In this study, serial sampling of CTCs (CellSearch system) was evaluated in 82 patients with metastatic BC enrolled in two randomized trials investigating ICI plus chemotherapy. Programmed death-ligand 1 (PD-L1) expression on CTCs was also measured. Patients with ≥ 2 CTCs per 7.5 mL at baseline had gene expression profiles in tumor suggestive of increased T-cell activity, including increased tumor inflammation signature (TIS) in both triple-negative (P = 0.010) and hormone receptor-positive (P = 0.024) disease. Patients with luminal A BC had higher CTC levels. The association between CTC status and outcome was most apparent 4 weeks into therapy. PD-L1 expression in CTCs was observed in 6/17 CTC-positive patients and was associated with inferior survival. In conclusion, our study indicates that CTC numbers may inform on tumor immune composition, as well as prognosis. These findings suggest a potential of using CTCs as an accessible biomarker source in BC patients treated with immunotherapy.© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.