Liquid Biopsy Assessment of Circulating Tumor Cell PD-L1 and IRF-1 Expression in Patients with Advanced Solid Tumors Receiving Immune Checkpoint Inhibitor.

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.

• Authors: Laura C Kennedy, Jun Lu, Sydney Kuehn, Arturo B Ramirez, Edward Lo, Yao Sun, Lance U'Ren, Laura Q M Chow, Zhengjia Chen, Petros Grivas, Eric P Kaldjian, Vijayakrishna K Gadi
• Journal: Targeted oncology (Target Oncol) Vol. 17 Issue 3 Pg. 329-341 (05 2022) ISSN: 1776-260X [Electronic] France
• PMID: 35696014 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Chemical References

• B7-H1 Antigen
• CD274 protein, human
• Immune Checkpoint Inhibitors
• Interferon Regulatory Factor-1

Topics

• B7-H1 Antigen
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Humans
• Immune Checkpoint Inhibitors
• Interferon Regulatory Factor-1 (metabolism)
• Liquid Biopsy
• Lung Neoplasms (drug therapy)
• Neoplastic Cells, Circulating (metabolism, pathology)
• Pilot Projects