CD169⁺ Macrophages in Primary Breast Tumors Associate with Tertiary Lymphoid Structures, T_regs and a Worse Prognosis for Patients with Advanced Breast Cancer

The presence of CD169⁺ macrophages in the draining lymph nodes of cancer patients is, for unknown reasons, associated with a beneficial prognosis. We here investigated the prognostic impact of tumor-infiltrating CD169⁺ macrophages in primary tumors (PTs) and their spatial relation to tumor-infiltrating B and T cells. Using two breast cancer patient cohorts, we show that CD169⁺ macrophages were spatially associated with the presence of B and T cell tertiary lymphoid-like structures (TLLSs) in both PTs and lymph node metastases (LNMs). While co-infiltration of CD169⁺/TLLS in PTs correlated with a worse prognosis, the opposite was found when present in LNMs. RNA sequencing of breast tumors further confirmed that SIGLEC1 (CD169) expression was associated with mature tertiary lymphoid structure (TLS), and T_reg and B_reg signatures. We propose that the negative prognostic value related to CD169⁺ macrophages in PTs is a consequence of an immunosuppressive tumor environment rich in TLSs, T_regs and B_regs.