journal contribution
posted on 2024-01-03, 08:21 authored by Jenna H. Rannikko, Petri Bono, Johanna Hynninen, Maija Hollmén MATINS trial pre-treatment biopsies used in this study, related to Figure
4G.
Funding
Horizon 2020 Framework Programme (H2020)
Cancer Foundations (Finland)
Academy of Finland (AKA)
Sigrid Juséliuksen Säätiö (Sigrid Jusélius Stiftelse)
Orionin Tutkimussäätiö (Orion Research Foundation)
Paulon Säätiö (Paulo Foundation)
History
ARTICLE ABSTRACT
Immune checkpoint inhibitors (ICI) show substantially greater efficacy in inflamed tumors characterized by preexisting T-cell infiltration and IFN signaling than in noninflamed “cold” tumors, which often remain immunotherapy resistant. The cancer immunotherapy bexmarilimab, which inhibits the scavenger receptor Clever-1 to release macrophage immunosuppression and activate adaptive immunity, has shown treatment benefit in subsets of patients with advanced solid malignancies. However, the mechanisms that determine bexmarilimab therapy outcome in individual patients are unknown. Here we characterized bexmarilimab response in ovarian cancer ascites macrophages ex vivo using single-cell RNA sequencing and demonstrated increased IFN signaling and CXCL10 secretion following bexmarilimab treatment. We further showed that bexmarilimab was most efficacious in macrophages with low baseline IFN signaling, as chronic IFNγ priming abolished bexmarilimab-induced TNFα release. These results highlight an approach to target immunologically cold tumors and to increase the likelihood of their subsequent response to ICIs.
