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- Title
Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma.
- Authors
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.
- 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. Immune checkpoint blockade therapy is successful in a high proportion of cancer patients, but others remain unresponsive. Authors here show that therapeutic success might be predictable in metastatic bladder cancer by longitudinal analysis of the early neoantigen-specific CD8 T cell response in peripheral blood.
- Subjects
TRANSITIONAL cell carcinoma; PROGRAMMED death-ligand 1; CD8 antigen; IMMUNE checkpoint proteins; CELLULAR recognition; T cells
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-29342-0