Targeting TNF-α-producing macrophages activates antitumor immunity in pancreatic cancer via IL-33 signaling.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) remains resistant to immune therapies, largely owing to robustly fibrotic and immunosuppressive tumor microenvironments. It has been postulated that excessive accumulation of immunosuppressive myeloid cells influences immunotherapy resistance, and recent studies targeting macrophages in combination with checkpoint blockade have demonstrated promising preclinical results. Yet our understanding of tumor-associated macrophage (TAM) function, complexity, and diversity in PDA remains limited. Our analysis reveals significant macrophage heterogeneity, with bone marrow-derived monocytes serving as the primary source for immunosuppressive TAMs. These cells also serve as a primary source of TNF-α, which suppresses expression of the alarmin IL-33 in carcinoma c

SUBMITTER: Dixit A 

PROVIDER: S-EPMC9746819 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature