Abstract Absolute count of circulating monocytes has been proposed as an independent prognostic factor in diffuse large B-cell lymphoma (DLBCL). However, monocyte nomenclature includes various subsets with pro-, anti-inflammatory, or suppressive functions, and their clinical relevance in DLBCL has been poorly explored. Herein, we broadly assessed circulating monocyte heterogeneity in 91 DLBCL patients. Classical- (cMO, CD14 pos CD16 neg ) and intermediate- (iMO, CD14 pos CD16 pos ) monocytes accumulated in DLBCL peripheral blood and exhibited an inflammatory phenotype. On the opposite, nonclassical monocytes (ncMO, CD14 low CD16 pos ) were decreased in peripheral blood. Tumor-conditioned monocytes presented similarities with ncMO phenotype from DLBCL and were prone to migrate in response to CCL3, CCL5, and CXCL12, and presented similarities with DLBCL-infiltrated myeloid cells, as defined by mass cytometry. Finally, we demonstrated the adverse value of an accumulation of nonclassical monocytes in 2 independent cohorts of DLBCL. Key points Nonclassical monocytes are prone to migrate to DLBCL tumor High count of circulating nonclassical monocytes is an independent adverse event in DLBCL

Nonclassical monocytes are prone to migrate into tumor in diffuse large B-cell lymphoma