以色列理工学院Yuval Shaked等研究人员合作发现，干扰素刺激的中性粒细胞是免疫疗法反应的预测指标。2024年1月4日，国际知名学术期刊《癌细胞》在线发表了这一成果。

研究人员发现干扰素刺激的Ly6E^hi中性粒细胞是小鼠基线抗PD1反应的血源性生物标志物。Ly6E^hi中性粒细胞是由肿瘤内在激活的STING（干扰素基因刺激因子）信号通路诱导的，部分通过IL12b依赖性激活细胞毒性T细胞，有能力直接使原本对抗PD1治疗无反应的肿瘤变得敏感。

通过将这些临床前研究结果转化为非小细胞肺癌和黑色素瘤患者队列（n=109）和公开数据（n=1440），研究人员证明了Ly6E^hi中性粒细胞能高精度（平均AUC≈0.9）地预测人类的免疫疗法反应。总之，这项研究确定了一种可用于小鼠和人类的具有功能活性的生物标记物。

据介绍，尽管抗癌免疫疗法取得了巨大成功，但其疗效仍局限于一部分患者，这就强调了预测性生物标志物在临床决策和进一步从机理上了解治疗反应中的重要性。然而，目前的生物标志物缺乏对患者进行准确分层所需的能力。

附：英文原文

Title: Interferon-stimulated neutrophils as a predictor of immunotherapy response

Author: Madeleine Benguigui, Tim J. Cooper, Prajakta Kalkar, Sagie Schif-Zuck, Ruth Halaban, Antonella Bacchiocchi, Iris Kamer, Abhilash Deo, Bar Manobla, Rotem Menachem, Jozafina Haj-Shomaly, Avital Vorontsova, Ziv Raviv, Chen Buxbaum, Petros Christopoulos, Jair Bar, Michal Lotem, Mario Sznol, Amiram Ariel, Shai S. Shen-Orr, Yuval Shaked

Issue&Volume: 2024-01-04

Abstract: 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, Ly6Ehi neutrophils as a blood-borne biomarker of anti-PD1 response in mice at baseline. Ly6Ehi 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 Ly6Ehi neutrophils to predict immunotherapy response in humans with high accuracy (average AUC ≈ 0.9). Overall, our study identifies a functionally active biomarker for use in both mice and humans.

DOI: 10.1016/j.ccell.2023.12.005

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00433-6