IFNγ PET Imaging as a Predictive Tool for Monitoring Response to Tumor Immunotherapy.

Autor:	Gibson HM; Department of Oncology, Karmanos Cancer Institute, Detroit, Michigan., McKnight BN; Department of Oncology, Karmanos Cancer Institute, Detroit, Michigan., Malysa A; Department of Oncology, Karmanos Cancer Institute, Detroit, Michigan., Dyson G; Department of Oncology, Karmanos Cancer Institute, Detroit, Michigan., Wiesend WN; Department of Anatomic Pathology, Beaumont Health System, Royal Oak, Michigan., McCarthy CE; Department of Oncology, Karmanos Cancer Institute, Detroit, Michigan., Reyes J; Department of Oncology, Karmanos Cancer Institute, Detroit, Michigan., Wei WZ; Department of Oncology, Karmanos Cancer Institute, Detroit, Michigan. villegan@karmanos.org weiw@karmanos.org., Viola-Villegas NT; Department of Oncology, Karmanos Cancer Institute, Detroit, Michigan. villegan@karmanos.org weiw@karmanos.org.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2018 Oct 01; Vol. 78 (19), pp. 5706-5717. Date of Electronic Publication: 2018 Aug 16.
DOI:	10.1158/0008-5472.CAN-18-0253
Abstrakt:	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. Cancer Res; 78(19); 5706-17. ©2018 AACR . (©2018 American Association for Cancer Research.)
Databáze:	MEDLINE
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