Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) presents significant diagnostic and prognostic challenges, as current biomarkers frequently fail to accurately stage disease, predict rapid metastatic recurrence (rPDAC), or assess response to neoadjuvant therapy (NAT). We investigated the potential for circulating neoplastic-immune hybrid cells (CHCs) as a non-invasive, multifunctional biomarker for PDAC. Methods: Peripheral blood specimens were obtained from patients diagnosed with PDAC. CHCs were detected by co-expression of pan-cytokeratin and CD45, normalized to 50,000 peripheral blood mononuclear cells. rPDAC was defined as metastatic recurrence within six months of margin-negative pancreatectomy. Cyclic immunofluorescence (CyCIF) analyses compared hybrid phenotypes in blood and tumors. Results: Blood samples were collected from 42 patients with PDAC prior to resection. Those with radiographically occult metastatic disease and rPDAC had higher preoperative CHC numbers compared to patients who did not (65.0 and 74.4, vs. 11.52 CHCs;p< 0.001). Patients with complete or near-complete pathologic responses to NAT had lower preoperative CHC numbers than partial and/or non-responders (1.7 vs. 13.1 CHCs;p= 0.008). When assessed longitudinally, those with partial pathologic response saw CHC levels become undetectable while on treatment but increase in the interval between NAT completion and resection. In contrast, patients with poor responses or development of metastatic disease experienced persistent CHC detection during therapy or rising levels prior to radiographic evidence of metastases. Further, in metastatic PDAC patients, treatment-induced phenotypic changes in hybrid cells mirrored those in paired metastatic tumor samples. Conclusions: CHC enumeration and phenotyping display promise as a real-time indicator of disease burden, recurrence risk, and treatment response in PDAC. CHCs have great potential as tumor-derived biomarkers to optimize therapeutic strategies and improve survival in patients with PDAC.
背景/目的：胰腺导管腺癌（PDAC）的诊断和预后评估面临重大挑战，当前生物标志物常难以准确分期、预测快速转移性复发（rPDAC）或评估新辅助治疗（NAT）反应。本研究探讨循环肿瘤-免疫杂合细胞（CHCs）作为PDAC无创多功能生物标志物的潜力。方法：采集PDAC确诊患者外周血样本，通过泛细胞角蛋白与CD45共表达检测CHCs，并以50,000个外周血单个核细胞为基准进行标准化。rPDAC定义为切缘阴性胰腺切除术后六个月内发生转移性复发。采用循环免疫荧光技术（CyCIF）对比血液与肿瘤组织的杂合细胞表型。结果：42例PDAC患者术前血液样本分析显示，影像学隐匿转移及rPDAC患者的术前CHC数量显著高于无转移患者（65.0和74.4对比11.52个CHCs；p<0.001）。对NAT达到完全或接近完全病理缓解的患者，其术前CHC数量低于部分缓解和/或无应答者（1.7对比13.1个CHCs；p=0.008）。纵向监测发现，部分缓解患者治疗期间CHC水平降至检测限以下，但在NAT结束至手术间隔期出现回升；而应答不佳或发生转移的患者在治疗期间持续检出CHC，或在影像学转移证据出现前呈现水平升高。此外，转移性PDAC患者中，治疗诱导的杂合细胞表型变化与配对转移瘤样本变化趋势一致。结论：CHC定量与表型分析有望成为PDAC疾病负荷、复发风险及治疗反应的实时监测指标，作为肿瘤源性生物标志物在优化治疗策略、改善患者生存方面具有巨大潜力。
肿瘤(癌症)患者之家