GSE99808 Transient activation of tumor-associated macrophages boosts anti-tumor immunity

Contributors : Sabine Hoves ; Chia-Huey Ooi
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Depletion of immunosuppressive tumor-associated macrophages (TAM) or reprogramming towards a pro-inflammatory activation state represent different strategies to therapeutically target this frequent myeloid population. Here we report that inhibition of colony-stimulating factor-1 receptor (CSF-1R) signaling sensitizes TAM to profound reprogramming in the presence of a CD40 agonist prior to their depletion. Despite the short-lived nature of macrophage hyperactivation, combined CSF-1R/CD40 stimulation of macrophages is sufficient to trigger a productive and durable T cell response in various mouse cancer models. The central role of macrophages in regulating T cell-dependent tumor rejections was substantiated by depletion experiments and transcriptomic analysis of ex vivo sorted TAM. Since CD40 expression on human TAM varies between different tumor types, co-expression of human CSF-1R and CD40 in colorectal adenocarcinoma and mesothelioma can serve as criteria to select these tumor types for clinical development

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2CCSAuG