This study examined the role of neutrophils in resistance to cancer immunotherapy (targeting T cells or myeloid cells) using neutropenic mice and genetic deletion models, focusing on how IFN-γ signaling controls neutrophil behavior.
Neutrophils primarily blocked immunotherapy responses by upregulating PD-L1 in an IFN-γ–dependent manner; specific deletion of *cd274* or *Ifngr1* on neutrophils eliminated this suppression and shifted neutrophils toward a pro-immunotherapy phenotype.
Findings are based on mouse models (neutropenic and genetic deletion); clinical translation to human tumors is not yet established. The paper does not report quantitative survival or response rate data. Broader generalizability across cancer types or immunotherapy classes is unclear.
Neutrophil PD-L1 expression, driven by cytotoxic lymphocyte–derived IFN-γ, appears to be a key resistance mechanism to cancer immunotherapy. Targeting neutrophil IFN-γ signaling or their PD-L1 may be a strategy to enhance immunotherapy efficacy, though clinical validation is needed.
Explore related topics
