Tumor-induced dendritic cell deregulation perturbs T cell proliferation and predicts clinical outcome in acute lymphoblastic leukemia.

Perturbations in dendritic cells (DCs) in B/T cell acute lymphoblastic leukemia (ALL), their cause(s) and consequence(s) on antileukemia immunity, and patient outcomes remain poorly explored. We find that maturation of DC1-6 subsets is disrupted in children and adults with ALL. Conventional DC1 and DC2 subpopulations are reduced at the expense of the progenitors and the DC4 fractions in ALL. The potential to mature, present antigens, and produce cytokines for initiating T cell surveillance appears to be impaired in every ALL DC subset. Such DC subsets are accordingly unable to induce T cell proliferation compared to DCs from healthy donors. MYC overexpression in ALL cells disrupts DC homeostasis and reduces the ability of DCs to induce T cell proliferation. Predominance of cells with transcriptional signatures typical of "stimulated DCs" predicts favorable clinical outcomes in B-ALL, while it is associated with unfavorable outcomes in T-ALL. Phenotyping DC subsets at ALL diagnosis could thus be valuable in informing treatment outcomes.