Science and Research

Interferon-stimulated neutrophils as a predictor of immunotherapy response

Despite the remarkable success of anti-cancer immunotherapy, its effectiveness remains confined to a subset of patients-emphasizing the importance of predictive biomarkers in clinical decision-making and further mechanistic understanding of treatment response. Current biomarkers, however, lack the power required to accurately stratify patients. Here, we identify interferon-stimulated, Ly6E(hi) neutrophils as a blood-borne biomarker of anti-PD1 response in mice at baseline. Ly6E(hi) neutrophils are induced by tumor-intrinsic activation of the STING (stimulator of interferon genes) signaling pathway and possess the ability to directly sensitize otherwise non-responsive tumors to anti-PD1 therapy, in part through IL12b-dependent activation of cytotoxic T cells. By translating our pre-clinical findings to a cohort of patients with non-small cell lung cancer and melanoma (n = 109), and to public data (n = 1440), we demonstrate the ability of Ly6E(hi) neutrophils to predict immunotherapy response in humans with high accuracy (average AUC 

  • Benguigui, M.
  • Cooper, T. J.
  • Kalkar, P.
  • Schif-Zuck, S.
  • Halaban, R.
  • Bacchiocchi, A.
  • Kamer, I.
  • Deo, A.
  • Manobla, B.
  • Menachem, R.
  • Haj-Shomaly, J.
  • Vorontsova, A.
  • Raviv, Z.
  • Buxbaum, C.
  • Christopoulos, P.
  • Bar, J.
  • Lotem, M.
  • Sznol, M.
  • Ariel, A.
  • Shen-Orr, S. S.
  • Shaked, Y.

Keywords

  • Biomarker
  • Sting
  • immunotherapy
  • interferon
  • melanoma
  • neutrophils
  • non-small cell lung cancer
  • response
Publication details
DOI: 10.1016/j.ccell.2023.12.005
Journal: Cancer Cell
Work Type: Original
Location: TLRC
Disease Area: LC
Partner / Member: Thorax
Access-Number: 38181798

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