Tumor-associated myeloid cells provide critical support for T-ALL in vivo

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Abstract T cell acute lymphoblastic leukemia (T-ALL) is a malignancy of immature T cells. Despite harboring multiple genetic alterations that drive disease, primary T-ALL cells require exogenous signals to survive. We previously reported that tumor-associated myeloid cells support survival of primary mouse T-ALL cells in vitro. However, the contribution of myeloid cells to T-ALL progression in vivo remains unclear. Here, we depleted phagocytic myeloid cells from leukemic mice, resulting in a significant reduction in tumor burden in multiple organs and prolonged survival. T-ALL burden also diminished following myeloid depletion in lymphodeficient mice, indicating that adaptive immunity was not required to eliminate T-ALL cells, thus suggesting tumor-associated myeloid cells could directly support T-ALL growth. Consistent with this possibility, multiple subsets of tumor-associated myeloid cells support survival of mouse and primary patient T-ALL cells in vitro. Acute myeloid depletion reduced activation of several pathways regulating cell survival in T-ALL cells, implicating these pathways in promoting T-ALL progression in vivo. Computational analysis of published datasets shows an association between enriched macrophage gene signatures and poor prognosis in T-ALL patients, further implicating a pro-tumor role for myeloid cells. Together, our results indicate that an altered myeloid compartment directly promotes T-ALL progression at divergent T-ALL sites in vivo.