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OtherBasic Science (Animal or Phantoms)

Dynamic Tumor-Specific MHC-II Immuno-PET Predicts Checkpoint Inhibitor Immunotherapy Efficacy in Melanoma

Zhen Yang, Feng Li, Yuqian Huang, Na Yin, Junjun Chu, Ying Ma, Roderic I Pettigrew, Dale Hamilton, Diego Martin and Zheng Li
Journal of Nuclear Medicine February 2022, jnumed.121.263151; DOI: https://doi.org/10.2967/jnumed.121.263151
Zhen Yang
1 Houston Methodist Academic Institute, United States;
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Feng Li
1 Houston Methodist Academic Institute, United States;
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Yuqian Huang
1 Houston Methodist Academic Institute, United States;
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Na Yin
2 Baylor College of Medicine;
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Junjun Chu
3 University of Southern California;
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Ying Ma
4 National Institutes of Health;
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Roderic I Pettigrew
5 Engineering Medicine, Texas A&M University
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Dale Hamilton
1 Houston Methodist Academic Institute, United States;
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Diego Martin
1 Houston Methodist Academic Institute, United States;
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Zheng Li
1 Houston Methodist Academic Institute, United States;
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Abstract

Despite the advance of immunotherapy, only a small subset of patients gains long-term survival benefit. It warrants a compelling rationale to develop immuno-PET imaging that could predict tumor response to the immunotherapy. An increasing number of studies have shown that tumor-specific major histocompatibility complex II (tsMHC-II) associates with improved responses to targeted immunotherapy. The aim of this study was to investigate the potential of tsMHC-II protein expression and its dynamic change upon treatment with interferon γ (IFNγ) as a new target for immuno-PET to predict response to immunotherapy. Methods: MHC-II antibody was radiolabeled with DOTA-chelated 64Cu to derive an MHC-II immuno-PET tracer. Two melanoma models models (B16SIY, B16F10), which are respondent and non-respondent to PD1/PD-L1 checkpoint inhibitor, respectively, were used. Both tumor models were treated with anti-PD1 and IFNγ, which enabled observation of dynamic change of tsMHC-II. Small-animal PET imaging, biodistribution and histological studies were performed to validate the correlation of tsMHC-II with the tumor response to the immunotherapy. Results: FACS analysis of the two tumors supported the consensual recognition of tsMHC-II correlated to the tumor response to the immunotherapy. The in vivo PET imaging revealed higher basal levels of tsMHC-II in the responder, B16SIY, than in the non-responder, B16F10. When treated with anti-PD1 antibody in animals, B16SIY tumors displayed a sensitive increase of tsMHC-II compared to B16F10 tumors. In IFNγ stimulation groups, the greater magnitude of tsMHC-II was further amplified when the IFNγ signaling is activated in the B16SIY tumors, which positively upregulates tsMHC-II in the tumor immunity. Subsequent histopathological analysis supported the correlative characteristics of tsMHC-II with tumor immunity and response to cancer immunotherapy. Conclusion: Collectively, the predictive value of tsMHC-II immuno-PET was validated for stratifying tumor immunotherapy responders vs. non-responders. Monitoring sensitivity of tsMHC-II to IFNγ stimulation may provide an effective strategy to predict the tumor response to immunotherapy.

  • Oncology: Melanoma
  • PET/CT
  • Radioimmunoimaging
  • MHC-II
  • anti-PD1 immunotherapy
  • immuno-PET
  • melanoma
  • molecular imaging
  • Copyright © 2022 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
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Journal of Nuclear Medicine: 64 (12)
Journal of Nuclear Medicine
Vol. 64, Issue 12
December 1, 2023
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Dynamic Tumor-Specific MHC-II Immuno-PET Predicts Checkpoint Inhibitor Immunotherapy Efficacy in Melanoma
Zhen Yang, Feng Li, Yuqian Huang, Na Yin, Junjun Chu, Ying Ma, Roderic I Pettigrew, Dale Hamilton, Diego Martin, Zheng Li
Journal of Nuclear Medicine Feb 2022, jnumed.121.263151; DOI: 10.2967/jnumed.121.263151

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Dynamic Tumor-Specific MHC-II Immuno-PET Predicts Checkpoint Inhibitor Immunotherapy Efficacy in Melanoma
Zhen Yang, Feng Li, Yuqian Huang, Na Yin, Junjun Chu, Ying Ma, Roderic I Pettigrew, Dale Hamilton, Diego Martin, Zheng Li
Journal of Nuclear Medicine Feb 2022, jnumed.121.263151; DOI: 10.2967/jnumed.121.263151
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Keywords

  • Oncology: Melanoma
  • PET/CT
  • Radioimmunoimaging
  • MHC-II
  • anti-PD1 immunotherapy
  • immuno-PET
  • melanoma
  • molecular imaging
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