Laura C Kennedy1,2,3, Jun Lu4,5, Sydney Kuehn6, Arturo B Ramirez7, Edward Lo7, Yao Sun7, Lance U'Ren7, Laura Q M Chow8,9, Zhengjia Chen4,5, Petros Grivas6,8, Eric P Kaldjian7, Vijayakrishna K Gadi6,8,10. 1. Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. laura.kennedy@vumc.org. 2. Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. laura.kennedy@vumc.org. 3. Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA. laura.kennedy@vumc.org. 4. Divison of Epidemiology and Biostatistics, University of Illinois, Chicago, IL, USA. 5. Biostatistics Shared Resource, University of Illinois Cancer Center, Chicago, IL, USA. 6. Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. 7. RareCyte, Inc., Seattle, WA, USA. 8. Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA. 9. Department of Oncology, University of Texas at Austin, Austin, TX, USA. 10. Department of Medicine, University of Illinois, Chicago, IL, USA.
Abstract
BACKGROUND: Reliable biomarkers that can be serially monitored to predict treatment response to immune checkpoint inhibitors (ICIs) are still an unmet need. Here, we present a multiplex immunofluorescence (IF) assay that simultaneously detects circulating tumor cells (CTCs) and assesses CTC expression of programmed death ligand-1 (PD-L1) and interferon regulatory factor 1 (IRF-1) as a candidate biomarker related to ICI use. OBJECTIVE: To assess the potential of CTC PD-L1 and IRF-1 expression as candidate biomarkers for patients with advanced epithelial solid tumors receiving ICIs. PATIENTS AND METHODS: We tested the IF CTC assay in a pilot study of 28 patients with advanced solid tumors who were starting ICI. Blood for CTC evaluation was obtained prior to starting ICI, after a single cycle of therapy, and at the time of radiographic assessment or treatment discontinuation. RESULTS: At baseline, patients with 0-1 CTCs had longer progression-free survival (PFS) compared to patients with ≥ 2 CTCs (4.3 vs 1.3 months, p = 0.01). The presence of any PD-L1+ CTCs after a single dose of ICI portended shorter PFS compared to patients with no CTCs or PD-L1- CTCs (1.2 vs 4.2 months, p = 0.02); the presence of any PD-L1+ or IRF-1+ CTCs at time of imaging assessment or treatment discontinuation also was associated with shorter PFS (1.9 vs 5.5 months, p < 0.01; 1.6 vs 4.7 months, p = 0.05). CTC PD-L1 and IRF-1 expression did not correlate with tumor tissue PD-L1 or IRF-1 expression. Strong IRF-1 expression in tumor tissue was associated with durable (≥ 1 year) radiographic response (p = 0.02). CONCLUSIONS: Based on these results, CTC PD-L1 and IRF-1 expression is of interest in identifying ICI resistance and warrants further study.
BACKGROUND: Reliable biomarkers that can be serially monitored to predict treatment response to immune checkpoint inhibitors (ICIs) are still an unmet need. Here, we present a multiplex immunofluorescence (IF) assay that simultaneously detects circulating tumor cells (CTCs) and assesses CTC expression of programmed death ligand-1 (PD-L1) and interferon regulatory factor 1 (IRF-1) as a candidate biomarker related to ICI use. OBJECTIVE: To assess the potential of CTC PD-L1 and IRF-1 expression as candidate biomarkers for patients with advanced epithelial solid tumors receiving ICIs. PATIENTS AND METHODS: We tested the IF CTC assay in a pilot study of 28 patients with advanced solid tumors who were starting ICI. Blood for CTC evaluation was obtained prior to starting ICI, after a single cycle of therapy, and at the time of radiographic assessment or treatment discontinuation. RESULTS: At baseline, patients with 0-1 CTCs had longer progression-free survival (PFS) compared to patients with ≥ 2 CTCs (4.3 vs 1.3 months, p = 0.01). The presence of any PD-L1+ CTCs after a single dose of ICI portended shorter PFS compared to patients with no CTCs or PD-L1- CTCs (1.2 vs 4.2 months, p = 0.02); the presence of any PD-L1+ or IRF-1+ CTCs at time of imaging assessment or treatment discontinuation also was associated with shorter PFS (1.9 vs 5.5 months, p < 0.01; 1.6 vs 4.7 months, p = 0.05). CTC PD-L1 and IRF-1 expression did not correlate with tumor tissue PD-L1 or IRF-1 expression. Strong IRF-1 expression in tumor tissue was associated with durable (≥ 1 year) radiographic response (p = 0.02). CONCLUSIONS: Based on these results, CTC PD-L1 and IRF-1 expression is of interest in identifying ICI resistance and warrants further study.
Authors: Luc Dirix; Andy Buys; Steffy Oeyen; Dieter Peeters; Vincent Liègeois; Annemie Prové; Dieter Rondas; Liesbet Vervoort; Véronique Mariën; Steven Van Laere; Peter Vermeulen Journal: Breast Cancer Res Treat Date: 2022-04-09 Impact factor: 4.624