Dynamic change of PD-L1 expression on circulating tumor cells in advanced breast cancer undergoing PD-1 blockade therapy.

Abstract

e14558 Background: PD-1/PD-L1 checkpoint blockade immunotherapy is revolution- izing the therapeutic strategy of malignancies. Tumor PD-L1 levels have predictive value in PD-1/PD-L1 checkpoint blockade therapies. Whether PD-L1 expression on circulating tumor cells (CTCs) could serve as an alternative biomarker is of great interest, especially in breast cancer. Methods: 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). 20patients with advanced breast cancerwere enrolled who took PD-1 inhibitortherapy. The CTC numeration and the PD-L1 expression levels were analyzedat the begining and ending of treatment . Results: 20 patients were enrolled, 85%(17/20) were triple-negative breast cancer. 65% of patients had visceral metastases, 60% of patients had ≥3 lines of treatment. Prior the treatment of PD-1 inhibitor, 95% (19/20) patients had CTCs, ranging from1 to 53(median 5). 90% (18/20) had PD-L1positive CTCs, and 75% (15/20) had at least one PD-L1high CTCs. The clinical benefit rate(CBR) rate in PD-L1high patients (26.7%) is much higher than the others (0%). we examined the proportion of PD-L1high CTCs relative to total CTCs. The median proportion of PD-L1high CTCs was 33.3%. Patients with ≥33% PD-L1high CTCs had a significantly longer PFS (median 2.6 vs. 1.4 months( P = 0.027). 100% patients with CBR had PD-L1highCTCs decreased and 46.7% of patients without CBR decreased. Further analysis showed that the mean proportion of PD-L1highCTCs at baseline and after treatment was 56.8±20.7%, 19.0±23.7%, p = 0.005. There was no significant difference in the mean proportion of PD-L1highCTCs before and after treatment in the non-CBR group (28.0±26.2%, 30.3±31.5%, p = 0.846). 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 PD-L1high CTCscould indicate the therapeutic response at early time.