What question did this study set out to answer?

This research aims to evaluate the relationship between PD-L1 expression in tumor macrophage fusion cells and patient outcomes in metastatic breast cancer receiving checkpoint inhibitors.

April 5, 2026

Abstract 1025: Monitoring PD-L1 in tumor macrophage fusion cells in blood correlates to PD-L1 checkpoint inhibitor responses in metastatic breast cancer

Key Points

This research aims to evaluate the relationship between PD-L1 expression in tumor macrophage fusion cells and patient outcomes in metastatic breast cancer receiving checkpoint inhibitors.
Conducted a prospective pilot study involving 43 patients with metastatic breast cancer before anti-PD-L1 treatment.
Isolated tumor macrophage fusion cells from peripheral blood samples at four time points using microfilters.
Measured PD-L1 expression in TMFCs and correlated it with progression-free survival and overall survival using statistical analyses.
Patients with high TMFC PD-L1 expression at T2 had significantly better progression-free survival.
No correlation was found between CPS and T0 TMFC PD-L1 levels.
High TMFC PD-L1 expression at any time point correlated with improved progression-free survival, suggesting its potential as a real-time biomarker for treatment response.

Abstract

Abstract In metastatic breast cancer (mBC), anti-PD-L1/PD-1 immune checkpoint inhibitors (ICIs), e.g. pembrolizumab, are approved in a subpopulation of mBC patients (pts) with a PD-L1 combined positive score (CPS) ≥10, median progression-free survival (mPFS) of 9.7 months and median overall survival (mOS) of 24 months. However, 62% of pts have CPS 10, and may also benefit from ICIs (i.e. ≥1 CPS have mPFS=7.6 months vs 5.6 for chemotherapy). One hypothesis to why low PD-L1 pts respond to ICIs is dynamic PD-L1 upregulation after starting a new therapy, requiring a biomarker to monitor PD-L1 and subsequent ICI benefit. Recent studies have identified PD-L1 expressing myeloid cells that disseminate into the blood from primary tumors, tumor-macrophage fusion cells (TMFCs), which may predict ICI response. However, dynamic changes in TMFC PD-L1 during ICI and their relationship to patient response is unknown. In this study, we monitored PD-L1 expression in TMFCs during ICI treatment, compared to tumor CPS, in mBC pts to evaluate PFS 30 µm) and polyploid nucleus. Average PD-L1 expressions in TMFCs were categorized as negative/low or high. Pearson’s correlation compared average TMFC PD-L1 to CPS PD-L1 from tissue. TMFC PD-L1 expression and CPS were compared to pts’ PFS and OS by Cox proportional univariate/multivariate analysis at 24 months. 95.3% (n=41/43) of pts provided a T0 sample. 90.7% (n=39/43) of pts provided a T1 sample (∼28 days after ICI). 67.4% (n=29/43) of pts provided a T2 sample (∼71 days), and 41.9% (n=18/43) of pts provided a T3 sample (∼117 days). mPFS of pts with CPS ≥10, 1-10, 1 was 8.5, 7.0, 2.0 months, respectively (≥10 CPS vs 10 CPS HR=1.5, p=0.9180), and mOS was 12.1, 9.0, 18.9 months (≥10 CPS vs 10 CPS HR=0.6, p=0.9981). No correlations were identified between CPS and T0 TMFC PD-L1 (p=0.6109). Further, pts with high TMFC PD-L1 at T2 (HR=3.1, p=0.0475) had significantly better PFS, while T1 (HR=1.8, p=0.1843) and T3 (HR=4.0, p=0.0686) trended toward better PFS, but not for OS. Pts with high TMFC PD-L1 at any time point had significantly improved PFS (HR=2.8, 95% CI=1.4-5.5, p=0.0052), but not OS, compared to pts with consistently low TMFC PD-L1. In this pilot study, tumor PD-L1 CPS was not found to be correlated with clinical outcomes. However, high TMFC PD-L1 expression at any timepoint correlated with improved PFS, suggesting that monitoring PD-L1 in TMFCs may serve as a real-time biomarker to better indicate ICI response. Further studies into the role of TMFC PD-L1 in predicting therapeutic response are ongoing. Citation Format: Sonia Muthuraj, Massimo Cristofanilli, Carolina Reduzzi, Giuseppe Del Priore, William V. Williams, Cha-Mei Tang, Daniel L. Adams. Monitoring PD-L1 in tumor macrophage fusion cells in blood correlates to PD-L1 checkpoint inhibitor responses in metastatic breast cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1025.

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