International Research Center, A.C. Camargo Cancer Center, São Paulo 01508-010, Brazil.
Department of Clinical Oncology, A.C. Camargo Cancer Center, São Paulo 01509-900, Brazil.
Int J Mol Sci. 2023 Jul 26;24(15):11958. doi: 10.3390/ijms241511958.
Circulating tumor cells (CTCs) and/or circulating tumor microemboli (CTM) from non-small cell lung cancer (NSCLC) patients may be a non-invasive tool for prognosis, acting as liquid biopsy. CTCs interact with platelets through the transforming growth factor-β/transforming growth factor-β receptor type 1 (TGF-β/TGFβRI) forming clusters. CTCs also may express the Cluster of Differentiation 47 (CD47) protein, responsible for the inhibition of phagocytosis, the "don't eat me" signal to macrophages.
To isolate, quantify and analyze CTCs/CTMs from metastatic NSCLC patients, identify TGFβRI/CD47 expression in CTCs/CTMs, and correlate with progression-free survival (PFS).
Blood (10 mL) was collected at two time-points: T1 (before the beginning of any line of treatment; T2 (60 days after initial collection). CTCs were isolated using ISET. Immunocytochemistry was conducted to evaluate TGFβRI/CD47 expression.
45 patients were evaluated. CTCs were observed in 82.2% of patients at T1 (median: 1 CTC/mL; range: 0.33-11.33 CTCs/mL) and 94.5% at T2 (median: 1.33 CTC/mL; 0.33-9.67). CTMs were observed in 24.5% of patients and significantly associated with poor PFS (10 months vs. 17 months for those without clusters; = 0.05) and disease progression ( = 0.017). CTMs CD47+ resulted in poor PFS ( = 0.041). TGFβRI expression in CTCs/CTMs was not associated with PFS.
In this study, we observed that CTC/CTM from NSCLC patients express the immune evasion markers TGFβRI/CD47. The presence of CTMs CD47+ is associated with poor PFS. This was the first study to investigate CD47 expression in CTCs/CTM of patients with NSCLC and its association with poor PFS.
从转移性非小细胞肺癌（NSCLC）患者中分离、定量和分析循环肿瘤细胞（CTC）/循环肿瘤微栓子（CTM），鉴定 CTC/CTM 中的转化生长因子-β/转化生长因子-β受体 1（TGF-β/TGFβRI）和 CD47 表达，并与无进展生存期（PFS）相关。
采集转移性 NSCLC 患者 2 个时间点的血液（10mL）：T1（在任何一线治疗开始前）；T2（初次采集后 60 天）。采用 ISET 法分离 CTCs。免疫细胞化学法检测 TGFβRI/CD47 表达。
共评估了 45 例患者。T1 时，82.2%的患者可观察到 CTCs（中位数：1 个 CTC/mL；范围：0.33-11.33 个 CTC/mL），T2 时，94.5%的患者可观察到 CTCs（中位数：1.33 个 CTC/mL；0.33-9.67 个 CTC/mL）。24.5%的患者可观察到 CTM，且 CTM 与较差的 PFS（有微栓子的患者为 10 个月，无微栓子的患者为 17 个月； = 0.05）和疾病进展（ = 0.017）显著相关。CTMs CD47+与较差的 PFS 相关（ = 0.041）。CTC/CTM 中的 TGFβRI 表达与 PFS 无关。
在本研究中，我们观察到 NSCLC 患者的 CTC/CTM 表达免疫逃逸标志物 TGFβRI/CD47。CTMs CD47+的存在与较差的 PFS 相关。这是首次研究 NSCLC 患者 CTC/CTM 中 CD47 的表达及其与较差 PFS 的相关性。
