1三軍總醫院 外科部 泌尿外科；2國防醫學院 醫學科學研究所
Determination of PD-L1 Expression in Circulating Tumor Cells of Clear Cell Renal Cell Carcinoma Patients and Correlation with Response to PD-1 Inhibitors
Pei-Jhang Chiang1, Chien-Chang Kao1,2, Tai-Lung Cha1,2, Sheng-Tang Wu1, En Meng1, Chih-Wei Tsao1, Chin-Li Chen1, Guang-Huan Sun1, Dah-Shyong Yu1, Sun-Yran Chang1, Ming-Hsin Yang1,2
1Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense
Medical Center, Taipei, Taiwan
2Graduate School of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
Objective: Whether the expression of programmed cell death ligand 1(PD-L1) is related to the efficacy of immune checkpoint inhibitors on patients with clear cell renal cell carcinoma (ccRCC) is of great interest, yet biopsies can only provide baseline information. Therefore, we explored PD-L1 expression on circulating tumor cells (CTCs) which holds potential to predict response to PD-1 inhibitors.
Methods: CTC analysis was performed in blood samples from 20 ccRCC patients. CTCs were isolated on the basis of cell surface marker by filtration through IsoFlux device, followed by identification according to validated morphology and immunofluorescence studies. The PD-L1 expression levels and the clinical correlation were also analyzed.
Results: Prior the treatment of PD-1 inhibitors, all patients had CTCs, ranging from 1 to 22 (median 7), 75% (15/20) had PD-L1+ CTCs. The percentage of PD-L1+CTCs did not correlate with the percentage of PD-L1+ in biopsies determined by immunohistochemistry. The disease control (DC) rate in PD-L1+ patients (73%, 11/15) is much higher than the others (0%, 0/5). We also observed that the count changes of total CTC, PD-L1+ CTC and PD-L1+ CTC correlate quite well with disease outcome.
Conclusions: We showed that the abundance of PD-L1+ CTCs at baseline can serve as a predictor to screen patients for PD-1 blockade therapies and the dynamic changes of CTC could monitor the therapeutic response. The study confirms the feasibility of CTC PD-L1 detection in peripheral blood and can be an individualized immunotherapy molecular biomarker exploring real-time.