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  • [Cancer Res.] IFNγ PET Imaging as a Predictive Tool for Monitoring Response to Tumor Immunotherapy.

    Karmanos Cancer Institute / Wei WZ*, Viola-Villegas NT*

  • 출처
    Cancer Res.
  • 등재일
    2018 Oct 1
  • 저널이슈번호
    78(19):5706-5717. doi: 10.1158/0008-5472.CAN-18-0253. Epub 2018 Aug 16.
  • 내용

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    Abstract
    IFNγ is an attractive target for imaging active antitumor immunity due to its function in the T-cell signaling axis. Here, we test an IFNγ immuno-PET (immunoPET) probe for its capacity to identify adaptive immunotherapy response after HER2/neu vaccination in both spontaneous salivary and orthotopic neu+ mouse mammary tumors. IFNγ immunoPET detected elevated cytokine levels in situ after vaccination, which inversely correlated with tumor growth rate, an indicator of response to therapy. In a model of induced T-cell anergy where CD8 T cells infiltrate the tumor, but upregulate PD-1, IFNγ tracer uptake was equivalent to isotype control, illustrating a lack of antitumor T-cell activity. The IFNγ immunoPET tracer detected IFNγ protein sequestered on the surface of tumor cells, likely in complex with the IFNγ receptor, which may explain imaging localization of this soluble factor in vivo Collectively, we find that the activation status of cytotoxic T cells is annotated by IFNγ immunoPET, with reduced off-target binding to secondary lymphoid tissues compared with imaging total CD3+ tumor-infiltrating lymphocytes. Targeting of soluble cytokines such as IFNγ by PET imaging may provide valuable noninvasive insight into the function of immune cells in situ Significance: This study presents a novel approach to monitor therapeutic outcomes via IFNγ-targeted positron emission tomography.

     


    Author information

    Gibson HM#1, McKnight BN#1, Malysa A1, Dyson G1, Wiesend WN2, McCarthy CE1, Reyes J1, Wei WZ3, Viola-Villegas NT3.
    1
    Department of Oncology, Karmanos Cancer Institute, Detroit, Michigan.
    2
    Department of Anatomic Pathology, Beaumont Health System, Royal Oak, Michigan.
    3
    Department of Oncology, Karmanos Cancer Institute, Detroit, Michigan. villegan@karmanos.org weiw@karmanos.org.
    #
    Contributed equally

  • 편집위원

    Zr-89 표지 anti-IFNγ PET 영상검사가 IFNγ 생산 부위를 찾아 낼 수 있음을 보여 주였고, 항종양 면역성능을 보여준 연구임. 핵의학 영상기법이 종양면역치료 평가에 이용될 수 있음을보여 준 연구로 면역치료 연구자와 핵의학 영상연구자에게 관심을 끌 수 있는 연구로 보임.

    2018-11-14 16:43:28

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