AI Insight
This case-control study profiled 16 immune checkpoint proteins in serum samples from 88 treatment-naive breast cancer patients and 49 healthy controls using a multiplex immunoassay platform. A seven-protein panel combining co-inhibitory and co-stimulatory checkpoint molecules achieved high diagnostic accuracy (AUC = 0.89), outperforming conventional biomarkers CA15-3 and CEA. Additionally, elevated baseline TIM-3 and PD-L1 levels were associated with chemotherapy resistance and shorter progression-free survival, while a distinct eight-protein signature characterized triple-negative breast cancer patients.
Why it matters
Blood-based immune checkpoint profiling could offer a minimally invasive alternative or complement to existing breast cancer diagnostic tools, with particular value for identifying triple-negative breast cancer, a subtype that currently lacks reliable biomarkers and carries a poor prognosis. If validated in larger prospective cohorts, these panels could inform earlier detection and treatment stratification decisions.
by Mouna Stayoussef, Azza Habel, Weili Xu, Mariem Bessaad, Hanen Bouaziz, Mouna Ayadi, Wassim Y. Almawi, Anis Larbi, Besma Yacoubi-Loueslati
Background
Immune checkpoints (ICs) are key regulators of anti-tumor immunity, yet their diagnostic potential as blood-based biomarkers in breast cancer (BC) remains insufficiently characterized. Comprehensive serum profiling using multiplex immunoassays may enable minimally invasive detection and molecular stratification, particularly for triple-negative breast cancer (TNBC).
Methods
Serum samples from 88 treatment-naïve BC patients and 49 age-matched controls were analyzed using a 16-analyte MILLIPLEX® immuno-oncology panel. Six co-inhibitory and ten co-stimulatory IC proteins were quantified. Diagnostic accuracy was assessed using ROC curves and logistic regression. Associations with TNBC subtype, chemotherapy response, and 6-month progression-free survival (PFS) were evaluated.
Results
Seven immune checkpoint proteins (LAG-3, BTLA, CD80, GITRL, CTLA-4, GITR, TLR-2) showed significant differential expression between BC patients and controls. A seven-protein panel demonstrated high diagnostic accuracy (AUC = 0.89; sensitivity 83%; specificity 86%), surpassing CA15−3 and CEA. TNBC patients exhibited a distinct eight-protein signature, with TIM-3, CTLA-4, and CD28 independently associated with TNBC classification. Elevated baseline TIM-3 and PD-L1 were associated with chemotherapy resistance and shorter PFS.
Conclusions
Comprehensive serum IC profiling identified biomarkers with strong diagnostic and subtype-discriminatory potential. These minimally invasive panels show potential for BC detection and TNBC stratification, pending validation in prospective and longitudinal studies. Validation in larger, multi-center cohorts is warranted.