A regulatory B cell subpopulation expressing CD301b lectin promotes breast cancer growth

Abstract

Aberrant tumor glycosylation can alter immune recognition; however, the specific influence of glycan-lectin interactions on tumor progression remains poorly understood. Here, we identify the C-type lectin receptor CD301b (encoded by Mgl2) as a regulator of immune activity within the breast tumor microenvironment (TME). Using a murine triple-negative breast cancer model, we demonstrate that tumors expressing the Tn glycoantigen grow more rapidly, and this growth is facilitated by CD301b immune cells. Depletion or genetic loss of CD301b markedly suppressed tumor growth, indicating that CD301b promotes tumor progression through myeloid-tumor interactions. Phenotypic analyses revealed that CD301b cells within tumors are type 2 conventional dendritic cells (cDC2s), a subset known to influence immune polarization. Single-cell RNA sequencing of human breast cancers showed that the human ortholog CLEC10A is expressed in cDC2-like dendritic cells and select macrophage subsets, suggesting a conserved role for CD301 myeloid populations. Transcriptomic profiling of tumors developed in Mgl2-deficient mice revealed a shift toward an inflammatory, immune-activated state consistent with enhanced antitumor immunity. Together, these findings establish a link between tumor glycosylation and lectin signaling of myeloid cells, highlighting CD301b as a potential target for reprogramming the tumor immune microenvironment in breast cancer.