Biology subjects

Gonzalez-Anton, S.

Publications and source records attributed to Gonzalez-Anton, S..

2 recordsLinked to original sources

bioRxiv2024

SIRPalpha+ PD-L1+ bone marrow macrophages aid AML growth by modulating T cell function

Acute myeloid leukemia (AML) continues to have a poor prognosis due to its ability to relapse following initial response to chemotherapy. While immunotherapies hold the promise to revolutionize cancer treatment, AML has been particularly challenging to target. It is therefore important to better understand the relationship between AML cells and immune cells within the bone marrow (BM) microenvironment, where this disease grows. Here we focus on non-malignant BM macrophages, and using a combination of intravital microscopy, flow cytometry, transcriptomics and functional analyses we identify a subpopulation of immunomodulatory BM macrophages (IMMs) with a unique profile and function during AML progression. While the majority of macrophages are already being lost at early infiltration, IMMs are locally enriched. They are capable of efferocytosis and support AML growth through inhibition of T cells. Enrichment of IMMs in the BM of patients developing early relapse indicates that future development of interventions that target IMMs development and function may improve AML patients outcome.

cancer biology↗

bioRxiv2020

Dynamic regulation of hierarchical heterogeneity in Acute Myeloid Leukemia serves as a tumor immunoevasion mechanism

Acute Myeloid Leukemia, a hematological malignancy with poor clinical outcome, is composed of hierarchically heterogeneous cells. We examine the contribution of this heterogeneity to disease progression in the context of anti-tumor immune responses and investigate whether these responses regulate the balance between stemness and differentiation in AML. Combining phenotypic analysis with proliferation dynamics and fate-mapping of AML cells in a murine AML model, we demonstrate the presence of a terminally differentiated, chemoresistant population expressing high levels of PDL1. We show that PDL1 upregulation in AML cells, following exposure to IFN{gamma} from activated T cells, is coupled with AML differentiation and the dynamic balance between proliferation, versus differentiation and immunosuppression, facilitates disease progression in the presence of immune responses. This microenvironment-responsive hierarchical heterogeneity in AML may be key in facilitating disease growth at the population level at multiple stages of disease, including following bone marrow transplantation and immunotherapy.

cancer biology↗