Neutrophils respond to immunotherapy by upregulating PD-L1 through interferon-gamma signaling in the tumor microenvironment, dampening T-cell activity.

In mouse melanoma and breast cancer models, removing neutrophils enhances immunotherapy efficacy, yielding smaller tumors and greater cytotoxic T cell activation within tumors.

The findings suggest that combining immune checkpoint blockade with strategies to counteract neutrophil-mediated suppression could boost immunotherapy outcomes.

The study was an international collaboration spanning Sweden, the United States, Germany, and China, with funding from NIH, the Swedish Cancer Society, and the Swedish Foundation for Strategic Research.

Researchers report no conflicts of interest in this multi-country collaboration supported by NIH and Swedish funding bodies.

The Immunity paper titled Neutrophil regulation of immunotherapy for cancer is controlled by type II interferon was published online on June 15, 2026.

Pei and colleagues’ study, published in Immunity (2026) with DOI 10.1016/j.immuni.2026.05.014, details neutrophil regulation of immunotherapy by type II interferon.

Analyses of tumor samples from lung cancer patients receiving immunotherapy show similar neutrophil PD-L1–related mechanisms, indicating translational relevance to humans.

The work reframes neutrophils as modulators of adaptive immunity in cancer, driven by the tumor microenvironment during therapy.

Clinical implications point to depleting neutrophils, inhibiting neutrophil-induced PD-L1, or modulating IFN-γ signaling to augment current immunotherapies.