2024年4月23日,來自尋百匯生物肖騰飛團隊在《細胞》發表了標題為”IGSF8 is an innate immune checkpoint and cancer immunotherapy target.“的研究成果。研究顯示IGSF8是一種先天免疫檢查點腫瘤免疫治療靶點。








  • IGSF8 is highly expressed on malignant cells with antigen presentation defects
  • IGSF8 interacts with NK receptors to suppress NK cell cytotoxicity
  • Anti-IGSF8 antibody increases NK cell killing of malignant cells?in?vitro
  • Anti-IGSF8 alone or in combination with anti-PD1 inhibits tumor growth?in?vivo


Antigen presentation defects in tumors are prevalent mechanisms of adaptive immune evasion and resistance to cancer immunotherapy, whereas how tumors evade innate immunity is less clear. Using CRISPR screens, we discovered that IGSF8 expressed on tumors suppresses NK cell function by interacting with human KIR3DL2 and mouse Klra9 receptors on NK cells. IGSF8 is normally expressed in neuronal tissues and is not required for cell survival?in?vitro?or?in?vivo. It is overexpressed and associated with low antigen presentation, low immune infiltration, and worse clinical outcomes in many tumors. An antibody that blocks IGSF8-NK receptor interaction enhances NK cell killing of malignant cells?in?vitro?and upregulates antigen presentation, NK cell-mediated cytotoxicity, and T?cell signaling?in?vivo. In syngeneic tumor models, anti-IGSF8 alone, or in combination with anti-PD1, inhibits tumor growth. Our results indicate that IGSF8 is an innate immune checkpoint that could be exploited as a therapeutic target.



Yulong Li, Xiangyang Wu, Caibin Sheng et al,? IGSF8 is an innate immune checkpoint and cancer immunotherapy target.DOI: 10.1016/j.cell.2024.03.039,Cell:最新IF:66.85




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