Characterization of B cell activation and spatial distribution in the tumor microenvironment of high-grade serous ovarian cancer

Objective To characterize the distribution and activation status of B cell subsets in tumor tissue and peripheral blood from patients with high-grade serous ovarian cancer (HGSOC) diagnosis, and to assess B cell alterations following neoadjuvant chemotherapy (NACT) in relation to clinical response. Methods This translational observational study enrolled patients with FIGO stage III–IV HGSOC from the MICO trial (NCT06272240). Tumor and peripheral blood samples were collected at baseline—during primary debulking surgery (PDS) or diagnostic laparoscopy—and at interval debulking surgery (IDS). Peritoneal biopsies and blood samples were also obtained from healthy controls. Multiparametric flow cytometry and immunohistochemistry were used to characterize B cell phenotype, localization, and dynamics. Clinical data (BRCA status, survival) were included in our analysis. Results Among the 30 evaluable patients, B cells accounted for 2–28% of tumor-infiltrating immune cells. Tumor tissues collected from HGSOC patients were enriched in CD19+ B lymphocytes, enriched in memory and antibody-secreting cells (ASCs), which were significantly more abundant compared to healthy controls. At baseline, circulating CD71+ B cells were significantly increased in HGSOC patients relative to healthy controls. Percentage of infiltrated B cells positive for CD21 was increased after NACT, suggesting functional maturation. Histological analysis showed that, after IDS, patients with better prognosis displayed B-cell clusters in both intratumoral and peritumoral regions; those who experienced early relapse did not. Conclusions Preliminary results regarding B-cell distribution and activation in HGSOC indicate dynamic changes that may correlate with clinical outcomes. Spatially organized B cells may serve as favorable immune indicators and biomarkers for treatment stratification.