ABSTRACT
Medication-related osteonecrosis of the jaw (MRONJ) has emerged as a complication of anti-resorptive medications. Despite its low incidence rate, this problem has gained attention in recent years due to its devastating consequences and lack of preventive strategy. The fact that MRONJ incidence has been exclusive to the jawbones, despite the systemic effect of anti-resorptive medications, could be a starting point to unravel the multifactorial pathogenesis of this condition. This review aims to negotiate the question of why the jawbone is more susceptible to MRONJ than other skeletal sites. Approaching the problem from this perspective could provide new directions for the prevention of MRONJ and expand our understanding of the unique oral microenvironment.
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.
