Dendritic cell dysfunction independently predicts poor prognosis in acute lymphoblastic leukemia

We have used scRNA-seq to evaluate the production and maturation of DC1-6 subsets to be disrupted in children and adults with ALL. While conventional DC1 and DC2 are reduced, cells within all DC subsets in patients have impaired antigen presentation and produce less cytokines needed for initiating T-cell surveillance than their normal counterparts in healthy people. ALL DCs are unable to induce T-cell proliferation. Overexpression of MYC in leukemia cells, in part by abrogating NK surveillance, disrupts DC homeostasis and reduces the ability of DCs to induce T-cell immunity. Importantly, immature, dysfunctional DCs with impaired antigen presentation independently predict poor prognosis in patients with high-risk ALL. Thus, phenotyping DC subsets in bone marrow or peripheral blood at ALL diagnosis or relapse could inform the course of treatment.