Expression of immune checkpoints on circulating tumor cells in men with metastatic prostate cancer (mPC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 191-191
Author(s):  
Tian Zhang ◽  
Rebecca Garland Austin ◽  
Sally E Park ◽  
Daniella Runyambo ◽  
Rengasamy Boominathan ◽  
...  
Keyword(s):  
Disease Progression ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Checkpoint Inhibitors ◽  
Abiraterone Acetate ◽  
Immune Checkpoints ◽  
Cancer Center ◽  
The Novel ◽  
Limited Efficacy ◽  
Patient Enrollment

191 Background: Most immune checkpoint inhibitors have shown limited efficacy in unselected men with mPC, and there is limited understanding about which immune checkpoints (ICs) are relevant in mPC. We evaluated ICs on the cell surface of circulating tumor cells (CTCs) in patients with mPC. Methods: Patients were enrolled prospectively at the Duke Cancer Center in three cohorts: A) mCRPC starting the novel androgen receptor inhibitors abiraterone acetate (AA) or enza with or without sipuleucel-T, B) mCRPC with disease progression after AA or enza, and C) metastatic castration sensitive PC. The Cellsearch platform was used to capture EpCAM- and CK-expressing CTCs and analyzed for PD-L1, PD-L2, B7-H3, and CTLA-4 expression at baseline, 12 weeks, and at further disease progression. Results: Through August 2017, we enrolled 4 subjects in cohort A, 7 in cohort B, and 3 in cohort C. CTCs were detectable in every cohort. At baseline, B7-H3 was the most prevalent IC on a per-patient basis (mean 96% in cohort A, and 100% in cohort B, and 88% in cohort C). PD-L1 was detected less frequently (cohort A mean 8%, cohort B mean 42%, and cohort C mean 67%), with evidence of heterogeneity of CTC PD-L1 expression between and within patients. PD-L1 was expressed on 8% of CTCs in cohort C and cohort A, as compared to 28% of CTCs in cohort B, while CTLA-4 expression was not identified in cohort C, 3% of cohort A, and 15% of cohort B. B7H3 was expressed on 68% of cohort C, 91% of cohort A, and 98% of cohort B. PD-L2 was expressed on 0-7% of CTCs overall. Conclusions: Patients with mPC can have detectable and heterogeneous ICs on CTCs, particularly PD-L1 and B7-H3, and these characteristics can be monitored over time. B7-H3 was the most prevalent IC on CTCs, regardless of disease state. Our preliminary data suggests that men with mCRPC post-enza/AA have higher levels of PD-L1 and CTLA-4 expression on their CTCs as compared with men with mHSPC and mCRPC prior to enza/AA. Patient enrollment and analysis are ongoing.

scholarly journals Expression of immune checkpoints on circulating tumor cells in men with metastatic prostate cancer

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Tian Zhang ◽  
Anika Agarwal ◽  
R. Garland Almquist ◽  
Daniella Runyambo ◽  
Sally Park ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Immune Checkpoint ◽  
Metastatic Prostate Cancer ◽  
Checkpoint Inhibitors ◽  
Unmet Need ◽  
Abiraterone Acetate ◽  
Immune Checkpoints ◽  
Disease States

Abstract Background A subset of men with metastatic prostate cancer (mPC) responds to immune checkpoint inhibitors, and there is an unmet need to predict those most likely to benefit. We characterized circulating tumor cells (CTCs) for expression of immune checkpoint ligands in men with mPC as a non-invasive biomarker of immune evasion and immunotherapy benefit. Methods Three cohorts of patients were enrolled: 1) men with mCRPC starting abiraterone acetate/prednisone or enzalutamide (pre-ARSI), 2) men with mCRPC who were progressing on enzalutamide or abiraterone acetate/prednisone (post-ARSI), and 3) men with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) starting androgen deprivation therapy. CTCs were captured using the CellSearch® system and stained for PD-L1, PD-L2, B7-H3, and CTLA-4 at baseline, on treatment, and disease progression. Summary statistics on mean CTCs per cohort, as well as rates of ligand positivity were used to analyze CTCs by cohort and by timepoint. Results Men in all cohorts and timepoints had prevalent CTC B7-H3 expression (> 80%). We found evidence for CTC PD-L1 expression across disease states, in which > 1 positive CTC or > 50% of CTCs were positive for PD-L1 in 40 and 30% of men with mHSPC, respectively, 60 and 20% of men with mCRPC pre-ARSI, and 70 and 30% of men with mCRPC post-ARSI. CTC PD-L2 expression was present in 20–40% of men in each disease state, while CTC CTLA-4 expression was rare, present in 20% of men with mCRPC pre-ARSI and 10% of men with mCRPC post-ARSI or with mHSPC. CTC immune checkpoint expression was heterogeneous within/between men and across disease states. Conclusions We have identified that CTCs from men with mPC heterogeneously express immune checkpoints B7-H3, PD-L1, PD-L2, and CTLA-4, and the detection of these immune checkpoints may enable monitoring on immunotherapy.

scholarly journals Covalent chemistry on nanostructured substrates enables noninvasive quantification of gene rearrangements in circulating tumor cells

2019 ◽  
Vol 5 (7) ◽  
pp. eaav9186 ◽  
Author(s):  
Jiantong Dong ◽  
Yu Jen Jan ◽  
Ju Cheng ◽  
Ryan Y. Zhang ◽  
Meng Meng ◽  
...  
Keyword(s):  
Disease Progression ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Chain Reaction ◽  
Biopsy Specimens ◽  
Copy Numbers ◽  
Polymerase Chain ◽  
Treatment Responses ◽  
Rapid Purification ◽  
Digital Polymerase Chain Reaction

Well-preserved mRNA in circulating tumor cells (CTCs) offers an ideal material for conducting molecular profiling of tumors, thereby providing a noninvasive diagnostic solution for guiding treatment intervention and monitoring disease progression. However, it is technically challenging to purify CTCs while retaining high-quality mRNA.Here, we demonstrate a covalent chemistry–based nanostructured silicon substrate (“Click Chip”) for CTC purification that leverages bioorthogonal ligation–mediated CTC capture and disulfide cleavage–driven CTC release. This platform is ideal for CTC mRNA assays because of its efficient, specific, and rapid purification of pooled CTCs, enabling downstream molecular quantification using reverse transcription Droplet Digital polymerase chain reaction. Rearrangements of ALK/ROS1 were quantified using CTC mRNA and matched with those identified in biopsy specimens from 12 patients with late-stage non–small cell lung cancer. Moreover, CTC counts and copy numbers of ALK/ROS1 rearrangements could be used together for evaluating treatment responses and disease progression.

scholarly journals Circulating Tumor Cells in Gastrointestinal Malignancies: Current Techniques and Clinical Implications

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Georg Lurje ◽  
Marc Schiesser ◽  
Andreas Claudius Hoffmann ◽  
Paul Magnus Schneider
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Disease Progression ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Response To Therapy ◽  
Clinical Implications ◽  
Gastrointestinal Malignancies ◽  
Progression Of Disease

Since their introduction more than 50 years by Engell, circulating tumor cells (CTCs) have been evaluated in cancer patients and their detection has been correlated with clinical outcome, in esophageal, gastric, and colorectal cancer. With the availability of refined technologies, the identification of CTCs from peripheral blood is emerging as a useful tool for the detection of malignancy, monitoring disease progression, and measuring response to therapy. However, increasing evidence suggests a variety of factors to be responsible for disease progression. The analysis of a single CTC marker is therefore unlikely to accurately predict progression of disease with sufficient resolution and reproducibility. Here we discuss the current concept of CTCs, summarize the available techniques for their detection and characterization, and aim to provide a comprehensive update on the clinical implications of CTCs in gastrointestinal (GI) malignancies.

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