Andresen Nikolai Kragøe, Røssevold Andreas Hagen, Borgen Elin, Schirmer Cecilie Bendigtsen, Gilje Bjørnar, Garred Øystein, Lømo Jon, Stensland Marius, Nordgård Oddmund, Falk Ragnhild Sørum, Mathiesen Randi R, Russnes Hege G, Kyte Jon Amund, Naume Bjørn
Department of Clinical Cancer Research, Oslo University Hospital, Norway.
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Norway.
Mol Oncol. 2024 Jul 8. doi: 10.1002/1878-0261.13675.
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.
免疫检查点抑制剂（ICIs）已被引入乳腺癌（BC）治疗中，因此需要更好的生物标志物来预测疗效。循环肿瘤细胞（CTCs）对BC具有预后价值，但在ICI治疗背景下，关于CTCs的知识有限。在本研究中，对82例转移性BC患者进行了CTCs（CellSearch系统）的连续采样评估，这些患者参加了两项研究ICI联合化疗的随机试验。还检测了CTCs上程序性死亡配体1（PD-L1）的表达。基线时每7.5 mL血液中CTCs≥2个的患者，其肿瘤的基因表达谱提示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）疾病中肿瘤炎症特征（TIS）增加。管腔A型BC患者的CTCs水平更高。CTCs状态与预后之间的关联在治疗4周时最为明显。在17例CTCs阳性患者中有6例观察到CTCs上的PD-L1表达，且其与较差的生存率相关。总之，我们的研究表明，CTCs数量可能反映肿瘤免疫组成以及预后。这些发现提示了在接受免疫治疗的BC患者中，将CTCs用作一种可获取的生物标志物来源的潜力。
