Tumor-draining lymph nodes in ovarian cancer lack germinal centers but harbor tumor-reactive memory B cells clonally linked to intra-tumoral B cells

The presence of B cells within high-grade serous ovarian cancer (HGSOC) tumors associates with favorable prognoses. We examined the contribution of tumor-draining lymph nodes (TDLNs) to the anti-tumor B cell response. Patient-derived TDLNs were largely devoid of active germinal center (GC) structures, plasma cells (PCs), and T follicular helper cells and were instead dominated by quiescent memory B cells (MBCs) that expressed mutated, class-switched antibodies reactive to ovarian tumor cells. GC B cells and PCs largely resided within the tumor, whereas classical class-switched MBCs were present both in the tumor and in matched TDLN samples. MBCs located in the TDLNs were clonally related to MBCs and PCs within the tumor. Increased frequencies of DC-SIGN⁺ macrophages in TDLNs were correlated with reduced presence of GC B cells, suggesting a regulatory role. Thus, in HGSOC, TDLNs fail to sustain active GC responses, serving instead as reservoirs of tumor-reactive memory B cells that contribute to the intra-tumoral B cell response.