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Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma

Author

Listed:
  • Jeppe Sejerø Holm

    (Experimental and Translational Immunology, Health Technology, Technical University of Denmark)

  • Samuel A. Funt

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Annie Borch

    (Experimental and Translational Immunology, Health Technology, Technical University of Denmark)

  • Kamilla Kjærgaard Munk

    (Experimental and Translational Immunology, Health Technology, Technical University of Denmark)

  • Anne-Mette Bjerregaard

    (Experimental and Translational Immunology, Health Technology, Technical University of Denmark)

  • James L. Reading

    (University College London Cancer Institute)

  • Colleen Maher

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College
    Parker Institute for Cancer Immunotherapy)

  • Ashley Regazzi

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Phillip Wong

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College
    Parker Institute for Cancer Immunotherapy)

  • Hikmat Al-Ahmadie

    (Memorial Sloan Kettering Cancer Center)

  • Gopa Iyer

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Tripti Tamhane

    (Experimental and Translational Immunology, Health Technology, Technical University of Denmark)

  • Amalie Kai Bentzen

    (Experimental and Translational Immunology, Health Technology, Technical University of Denmark)

  • Nana Overgaard Herschend

    (Experimental and Translational Immunology, Health Technology, Technical University of Denmark)

  • Susan Wolf

    (Memorial Sloan Kettering Cancer Center)

  • Alexandra Snyder

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Taha Merghoub

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College
    Parker Institute for Cancer Immunotherapy)

  • Jedd D. Wolchok

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College
    Parker Institute for Cancer Immunotherapy
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Morten Nielsen

    (Health Technology, Technical University of Denmark)

  • Jonathan E. Rosenberg

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Dean F. Bajorin

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Sine Reker Hadrup

    (Experimental and Translational Immunology, Health Technology, Technical University of Denmark)

Abstract

CD8+ T cell reactivity towards tumor mutation-derived neoantigens is widely believed to facilitate the antitumor immunity induced by immune checkpoint blockade (ICB). Here we show that broadening in the number of neoantigen-reactive CD8+ T cell (NART) populations between pre-treatment to 3-weeks post-treatment distinguishes patients with controlled disease compared to patients with progressive disease in metastatic urothelial carcinoma (mUC) treated with PD-L1-blockade. The longitudinal analysis of peripheral CD8+ T cell recognition of patient-specific neopeptide libraries consisting of DNA barcode-labelled pMHC multimers in a cohort of 24 patients from the clinical trial NCT02108652 also shows that peripheral NARTs derived from patients with disease control are characterised by a PD1+ Ki67+ effector phenotype and increased CD39 levels compared to bystander bulk- and virus-antigen reactive CD8+ T cells. The study provides insights into NART characteristics following ICB and suggests that early-stage NART expansion and activation are associated with response to ICB in patients with mUC.

Suggested Citation

  • Jeppe Sejerø Holm & Samuel A. Funt & Annie Borch & Kamilla Kjærgaard Munk & Anne-Mette Bjerregaard & James L. Reading & Colleen Maher & Ashley Regazzi & Phillip Wong & Hikmat Al-Ahmadie & Gopa Iyer & , 2022. "Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29342-0
    DOI: 10.1038/s41467-022-29342-0
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