Low-Density Neutrophils dynamics as a potential biomarker for immunotherapy response in Breast Cancer patients: A Case Report

Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options. Although immunotherapy has improved outcomes in selected patients, predictive biomarkers remain scarce. Low-density neutrophils (LDNs), a subpopulation of immunosuppressive neutrophils, have been implicated in resistance to immune checkpoint inhibitors (ICIs), but their longitudinal dynamics and correlation with clinical parameters and immune markers have not been investigated to date, especially in TNBC. We report a case of a 48-year-old woman with early-stage TNBC treated with neoadjuvant chemoimmunotherapy per the KEYNOTE-522 protocol. Circulating LDNs, following density gradient centrifugation, as well as activation status of systemic T lymphocytes, were monitored longitudinally by flow cytometry. Parallel assessments included lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), cancer antigen 15.3 (CA 15.3), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR). Tumor-infiltrating lymphocytes (TILs) were characterized by immunohistochemistry, in the surgical specimen. LDNs were absent at baseline but increased during neoadjuvant therapy, peaking before radiologic progression and remaining elevated during palliative treatment. Notably, systemic T lymphocytes markers, such as CD69 and HLA-DR, declined as LDNs rose. This trajectory preceded disease evolution while conventional markers, such as LDH, CA 15.3, PLR and NLR rose later. The patient progressed during adjuvant immunotherapy and partially responded to first-line antibody-drug conjugate therapy. In line with the systemic immunosuppression profile, and resistance to immunotherapy, TIL analysis revealed low CD8 + infiltration and sparse CD20 + B cells. This case illustrates the potential of LDNs as minimally invasive biomarkers for monitoring treatment response and detecting therapy resistance in breast cancer (BC). Their longitudinal profile captured disease progression more precisely than conventional markers, underscoring their translational relevance for patient stratification and therapeutic guidance. Although limited by the single-patient design, these findings warrant investigation of LDNs dynamics in larger cohorts to validate their predictive value and clinical utility in optimizing immunotherapy outcomes in BC.