2026-06-15 カロリンスカ研究所（KI）
＜関連情報＞
- https://news.ki.se/some-immune-cells-can-limit-the-effect-of-cancer-immunotherapy
- https://www.cell.com/immunity/abstract/S1074-7613(26)00225-6
がんに対する免疫療法の好中球による調節はII型インターフェロンによって制御される Neutrophil regulation of immunotherapy for cancer is controlled by type II interferon
Shengduo Pei (裴圣多) ∙ Yueyun Pan (潘越芸) ∙ Heng Liang (梁恒) ∙ … ∙ Jeffrey V. Ravetch ∙ Oliver Soehnlein ∙ Mikael C.I. Karlsson
Immunity Published:June 15, 2026
DOI:https://doi.org/10.1016/j.immuni.2026.05.014
Graphical abstract
Highlights
- Neutrophil depletion enhances the treatment efficacy of cancer immunotherapy
- Immunotherapy-induced IFN-γ drives neutrophils to an aged and PD-L1-expressing phenotype
- Specific deletion of PD-L1 or IFN-γR stops development of immunosuppressive neutrophils
- Human tumors accumulate aged and PD-L1-expressing neutrophils after immunotherapy
Summary
Tumor resistance to immunotherapy is driven by several mechanisms, including those imposed by myeloid populations. Neutrophils are prominent within this landscape and display functional heterogeneity. Here, we investigated the contextual role of neutrophils, and using neutropenic mice, we found that the dominating function was to block the response when targeting T cells or myeloid cells. We found that neutrophils upregulated programmed death ligand-1 (PD-L1) in response to the treatment and, using this as a target, depleted this population. The upregulation of PD-L1 was dependent on interferon-γ (IFN-γ) produced by cytotoxic lymphocytes. Specific genetic deletion of cd274 or Ifngr1 on neutrophils showed that this was cell intrinsic. Moreover, in the absence of the capacity for specific IFN-γ-driven suppression, neutrophils changed their phenotype to support immunotherapy. Thus, we find that the type II interferon, IFN-γ, is key in determining whether neutrophils will support or block immunotherapy for cancer.
