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

• Published in: The Journal of immunology (1950) Vol. 204; no. 1_Supplement; pp. 163 - 163.5
• Main Authors: Lyu, Aram, Triplett, Todd A., Godfrey, Wesley H., Nam, Seo Hee, Ames, Rachel Y., Hu, Zicheng, Sarang, Adviti, Selden, Hilary J., Lee, Chang-Han, Georgiou, George, Horton, Terzah M., Ehrlich, Lauren I. R.
• Format: Journal Article
• Language: English
• Published: 01.05.2020
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.204.Supp.163.5

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.