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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

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9001725/
https://www.ncbi.nlm.nih.gov/pubmed/35410325
http://dx.doi.org/10.1038/s41467-022-29342-0
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author 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
author_facet 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
author_sort Holm, Jeppe Sejerø
collection PubMed
description 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.
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spelling pubmed-90017252022-04-27 Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma 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 Nat Commun Article 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. Nature Publishing Group UK 2022-04-11 /pmc/articles/PMC9001725/ /pubmed/35410325 http://dx.doi.org/10.1038/s41467-022-29342-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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
title Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma
title_full Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma
title_fullStr Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma
title_full_unstemmed Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma
title_short Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma
title_sort neoantigen-specific cd8 t cell responses in the peripheral blood following pd-l1 blockade might predict therapy outcome in metastatic urothelial carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9001725/
https://www.ncbi.nlm.nih.gov/pubmed/35410325
http://dx.doi.org/10.1038/s41467-022-29342-0
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