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Holm, Jeppe Sejerø; Funt, Samuel A.; Borch, Annie; Munk, Kamilla Kjærgaard; Bjerregaard, Anne-Mette; Reading, James L.; Maher, Colleen; Regazzi, Ashley; Wong, Phillip; Al-Ahmadie, Hikmat; Iyer, Gopa; Tamhane, Tripti; Bentzen, Amalie Kai; Herschend, Nana Overgaard; De Wolf, Susan; Snyder, Alexandra; Merghoub, Taha; Wolchok, Jedd D.; Nielsen, Morten; Rosenberg, Jonathan E.; Bajorin, Dean F.; Hadrup, Sine Reker

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

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  • Medientyp: E-Artikel
  • Titel: Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma
  • Beteiligte: Holm, Jeppe Sejerø; Funt, Samuel A.; Borch, Annie; Munk, Kamilla Kjærgaard; Bjerregaard, Anne-Mette; Reading, James L.; Maher, Colleen; Regazzi, Ashley; Wong, Phillip; Al-Ahmadie, Hikmat; Iyer, Gopa; Tamhane, Tripti; Bentzen, Amalie Kai; Herschend, Nana Overgaard; De Wolf, Susan; Snyder, Alexandra; Merghoub, Taha; Wolchok, Jedd D.; Nielsen, Morten; Rosenberg, Jonathan E.; Bajorin, Dean F.; Hadrup, Sine Reker
  • Erschienen: Springer Science and Business Media LLC, 2022
  • Erschienen in: Nature Communications, 13 (2022) 1
  • Sprache: Englisch
  • DOI: 10.1038/s41467-022-29342-0
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>CD8<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup> Ki67<jats:sup>+</jats:sup> effector phenotype and increased CD39 levels compared to bystander bulk- and virus-antigen reactive CD8<jats:sup>+</jats:sup> 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.</jats:p>
  • Zugangsstatus: Freier Zugang