Matthew Witkowski “The Evolving Immune Landscape of B cell Acute Lymphoblastic Leukaemia

Abstract:
While the outcomes for pediatric ALL now approach 90%, this disease remains a leading cause of cancer-related death in children. Outgrowth of tumor subclones with genetic and epigenetic lesions underpin tumor escape from both conventional and immunotherapies. Targeting a genetically stable supportive microenvironment is one promising avenue to overcome this roadblock. Here, we describe dynamic shifts in cellular composition of the leukemia-associated bone marrow immune microenvironment throughout B-ALL progression, and highlight the predictive value of leukemia-specific monocyte abundance in B-ALL patient survival. We demonstrate B-ALL promotes non-classical monocyte emergence, and that targeting leukemia-associated monocytes in combination with targeted therapy leads to prolonged disease remission in vivo. This study identifies monocytes as a potential targetable component of the leukemic immune microenvironment.

Publication available at Cancer Cell:
https://www.cell.com/cancer-ce....ll/fulltext/S1535-61