<p>Accumulating evidence has revealed that myeloid-derived suppressor cells (MDSCs) play a pivotal role in the poor prognosis of diffuse large B-cell lymphoma (DLBCL). The immunophenotypic profile of G-MDSCs is more complex and remains to be fully clarified. Our preliminary studies have discovered a novel population of CD10⁻negative neutrophils characterized by an immature phenotype and immunosuppressive properties, closely resembling those of G-MDSCs (named as CD10⁻G-MDSCs). Here, we investigated the expression profiles and disease relevance of CD10⁻G-MDSCs in DLBCL patients. The proportion of CD10⁻G-MDSCs in peripheral blood was prospectively analyzed by flow cytometry in 150 DLBCL patients and 40 healthy donors (HDs). Additionally, cytokine levels were measured in serum samples in 39 DLBCL patients. The levels of CD10⁻G-MDSCs were elevated in all DLBCL subgroups. Furthermore, the levels were particularly higher in the newly diagnosed (ND) and relapsed/refractory group compared to those in the remission group. In DLBCL-ND group, CD10⁻G-MDSCs expansion was closely associated with advanced stage, extranodal involvement, bulky mass, elevated LDH levels and double expression. Stratification by the median value (11.13%) showed that higher CD10⁻G-MDSCs levels were associated with poorer treatment response, progression-free survival and overall survival. CD10⁻G-MDSCs levels also were correlated positively with serum IL-6 and IL-17. Elevated circulating CD10⁻G-MDSCs were associated with adverse clinical features and poor outcomes in DLBCL. These findings suggest that CD10⁻G-MDSCs may serve as an adjunct marker for risk assessment. The correlation with pro-inflammatory cytokines raises the possibility of immunological involvement.</p>