循環腫瘤細胞之免疫檢查點生物標記作為泌尿上皮癌治療反應的潛在預測因子

賴姿君¹、查岱龍^1,2、蔡易達²、劉書瑜²、吳勝堂¹、蒙恩¹、曹智惟¹、高建璋¹、陳進利¹、孫光煥¹、于大雄¹、張聖原¹、楊明昕^1,2

¹國防醫學院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

Immune Checkpoint Biomarker on Circulating Tumor Cells as a Potential Predictor of Therapeutic Efficacy in Urothelial Carcinoma Patients

Tzu-Chun Lai¹, Tai-Lung Cha^1,2, Yi-Ta Tsai^1,2, Shu-Yu Liu¹, Sheng-Tang Wu¹, En Meng¹, Chih-Wei Tsao¹, Chien-Chang Kao^1,2, Chin-Li Chen¹, Guang-Huan Sun¹, Dah-Shyong Yu¹, Sun-Yran Chang¹, Ming-Hsin Yang^1,2

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

Background:

Programmed cell death ligand 1 (PD-L1) inhibitors are routinely used for the treatment of advanced urothelial carcinoma (UC). Whether PD-L1 is correlated to the efficacy of treatment on patients is of great interest, yet primary tumour biopsies can only provide limited information. Therefore, we explored PD-L1 expression on circulating tumour cells (CTCs) which are potential predictors of response to PD-L1 inhibitors.

Materials and Methods:

Blood samples were collected from 23 UC patients. CTCs were enriched on the basis of cell surface marker targeting to UC by IsoFlux device, followed by identification according to cell morphology and immunofluorescence (IF) studies. The PD-L1 expression status and the clinical correlation were also analysed.

Results:

Before the treatment of PD-L1 inhibitors, CTCs were detected in all patients, ranging from 1 to 7 (median 3), 65% (15/23) had PD-L1+ CTCs. The expression of PD-L1+ CTCs did not correlate with the immunohistochemistry staining (IHC) of PD-L1 in primary tumour biopsies. The disease control rate (DC) in patients with PD-L1+ CTCs (73%, 11/15) is much higher than the rate in others (13%, 1/8). We also found that the number changes of PD-L1+ CTC correlate well with the disease outcome.

Conclusions:

We showed that the existence of PD-L1+CTCs is a predictor for anti-PD-L1 treatment and the dynamic changes of PD-L1+ CTC counts could monitor the therapeutic response. Our study confirms the possibility of PD-L1+ CTC detection in UC patients’ blood samples and can be an individualized immunotherapy molecular biomarker exploring real-time.