Myeloid cell-based delivery of IFN-γ reprograms the leukemia microenvironment and induces anti-tumoral immune responses.

ABSTRACT: The immunosuppressive microenvironment surrounding tumor cells represents a key cause of treatment failure. Therefore, immunotherapies aimed at reprogramming the immune system have largely spread in the past years. We employed gene transfer into hematopoietic stem and progenitor cells to selectively express anti-tumoral cytokines in tumor-infiltrating monocytes/macrophages. We show that interferon-γ (IFN-γ) reduced tumor progression in mouse models of B-cell acute lymphoblastic leukemia (B-ALL) and colorectal carcinoma (MC38). Its activity depended on the immune system's capacity to respond to IFN-γ and drove the counter-selection of leukemia cells expressing surrogate antigens. Gene-based IFN-γ delivery induced antigen presentation in the myeloid compartment and on leukemia cells, leading

SUBMITTER: Mucci A 

PROVIDER: S-EPMC8495462 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature