Journal
ONCOIMMUNOLOGY
Volume 7, Issue 7, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2018.1438111
Keywords
advanced solid tumor; circulating tumor cells (CTCs); immunotherapy; programmed death-ligand 1 (PD-L1); semi-quantitative analysis
Categories
Funding
- Key Research Program of the Chinese Academy of Sciences [KFZD-SW-210]
- Beijing Municipal Science and Technology Project [Z171100002017013]
- Strategic Priority Research Program of Chinese Academy of Sciences [XDA09040300]
- National Natural Science Foundation of China [21775031, 81500900, 21503054]
- Beijing Talents Fund [2015000021223ZK36]
- Beijing Municipal Natural Science Foundation [L172035, 2172056]
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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-L1(negative), PD-L1(low), PD-L1(medium) and PD-L1(high)). 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-L1(positive) CTCs, and 60% (21/35) had at least one PD-L1(high) CTCs. The disease control (DC) rate in PD-L1(high) patients (48%) is much higher than the others (14%). The group with at least 20% abundance of PD-L1(high) 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-L1(postive) CTC and PD-L1(high) CTC correlate quite well with disease outcome (P<0.001, P = 0.002 and 0.007, respectively). In addition, the abundance of PD-L1(high) CTCs at baseline had predicative significance for progression free survival (PFS).Conclusions: We revealed that the abundance of PD-L1(high) 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.
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