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.