Dynamic change of PD-L1 expression on circulating tumor cells in advanced solid tumor patients undergoing PD-1 blockade therapy

Abstract

Background: Tumor PD-L1 levels have predictive value in PD-1/PD-L1 checkpoint blockade therapies, yet biopsies can only provide baseline information. Whether PD-L1 expression on circulating tumor cells (CTCs) could serve as an alternative biomarker is of great interest.Design: We established an immunofluorescence assay for semi-quantitative assessment of the PD-L1 expression levels on CTCs with four categories (PD-L1negative, PD-L1low, PD-L1medium and PD-L1high). 35 patients with different advanced gastrointestinal tumors were enrolled in a phase 1 trial of a PD-1 inhibitor, IBI308. The CTC numeration and the PD-L1 expression levels were analyzed.Results: Prior the treatment of IBI308, 97% (34/35) patients had CTCs, ranging from1 to 70 (median 7). 74% (26/35) had PD-L1positive CTCs, and 60% (21/35) had at least one PD-L1high CTCs. The disease control (DC) rate in PD-L1high patients (48%) is much higher than the others (14%). The group with at least 20% abundance of PD-L1high CTCs had even higher DC rate of 64% (9/14), with only 14% DC rate for the rest (3/21). We also observed that the count changes of total CTC, PD-L1postive CTC and PD-L1high CTC correlate quite well with disease outcome (P<0.001, P = 0.002 and 0.007, respectively). In addition, the abundance of PD-L1high CTCs at baseline had predicative significance for progression free survival (PFS).Conclusions: We revealed that the abundance of PD-L1high CTCs at baseline might serve as a predictor to screen patients for PD-1/PD-L1 blockade therapies and measuring the dynamic changes of CTC could indicate the therapeutic response at early time.

Tracking cancer progression: from circulating tumor cells to metastasis

“…Further, another study has recently developed a prognosis index-based on a CTC-derived gene expression signature composed of matrisome genes-that is associated with metastasis in NSCLC [77]. Concerning prediction of response to immunotherapy, expression of PD-L1 has also been evaluated in CTCs from patients who have various cancer types [125][126][127]. Together, these studies represent exciting proof-of-concept examples of how biomarker analyses in CTCs can be used to stratify patients prior to therapy initiation and of how CTCs can be used as a prognostic tool.…”

Emerging Role of Circulating Tumor Cells in Gastric Cancer

“…Moreover, the dynamic changes of PD-L1 positive CTCs can reflect real time response status. Indeed, in Yue's study [62], the count changes of total CTCs, PD-L1 positive CTC, and PD-L1 high CTC significantly correlated with the clinical outcomes ( Figure 1). This is an advantage of CTC PD-L1 over tumor PD-L1, which can only provide baseline information for treatment response prediction.…”

“…When CTC PD-L1 has been recognized as a biomarker for therapeutic efficacy of immune checkpoint inhibition in non-small cell lung cancer (NSCLC), it is unclear whether it can be a predictive marker for GC immune checkpoint therapy [100,101]. Along this line, Yue et al [62] demonstrated that PD-L1 level in CTCs can be a potential predictor for PD-1/PD-L1 blockade therapies in patients with advanced gastrointestinal tumors. The disease control (DC) rate in the patients with high CTC PD-L1 level was much higher than those with lower level.…”

Prospect of liquid biopsy application for precise medication of PD-1/PD-L1 inhibitor

“…肿瘤免疫治疗近年来备受关注, 是肿瘤治疗领 域的最大进展, 代表性的药物即为PD-1/PD-L1抑制 剂 [11] . 目前PD-1/PD-L1抑制剂已经在FDA获批多个 适应症, 分别是恶性黑色素瘤、非小细胞肺癌、肾细 胞癌、经典型霍奇金淋巴瘤、尿路上皮癌、结直肠癌、 胃癌和肝癌等 [12] . 在正常机体中, PD-L1(programmed cell death-Ligand 1, 程序性死亡受体-配体1)是一种 表达于细胞表面的蛋白, 又称B7-H1蛋白.…”

“…"PD-L1高表达(PD-L1 +++)的CTC的比例可用于 预测PD-1单药治疗效果"是军事医学科学院徐建明和 中国科学院研究团队 [12] 针对我国自主研发的PD-1单 技术进行CTC的捕获 [33,34] ,…”