IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29342-0.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29342-0
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-29342-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Matthew M. Gubin & Xiuli Zhang & Heiko Schuster & Etienne Caron & Jeffrey P. Ward & Takuro Noguchi & Yulia Ivanova & Jasreet Hundal & Cora D. Arthur & Willem-Jan Krebber & Gwenn E. Mulder & Mireille T, 2014. "Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens," Nature, Nature, vol. 515(7528), pages 577-581, November.
    2. Elise Alspach & Danielle M. Lussier & Alexander P. Miceli & Ilya Kizhvatov & Michel DuPage & Adrienne M. Luoma & Wei Meng & Cheryl F. Lichti & Ekaterina Esaulova & Anthony N. Vomund & Daniele Runci & , 2019. "MHC-II neoantigens shape tumour immunity and response to immunotherapy," Nature, Nature, vol. 574(7780), pages 696-701, October.
    3. Vinod P. Balachandran & Marta Łuksza & Julia N. Zhao & Vladimir Makarov & John Alec Moral & Romain Remark & Brian Herbst & Gokce Askan & Umesh Bhanot & Yasin Senbabaoglu & Daniel K. Wells & Charles Ia, 2017. "Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer," Nature, Nature, vol. 551(7681), pages 512-516, November.
    4. Paul C. Tumeh & Christina L. Harview & Jennifer H. Yearley & I. Peter Shintaku & Emma J. M. Taylor & Lidia Robert & Bartosz Chmielowski & Marko Spasic & Gina Henry & Voicu Ciobanu & Alisha N. West & M, 2014. "PD-1 blockade induces responses by inhibiting adaptive immune resistance," Nature, Nature, vol. 515(7528), pages 568-571, November.
    5. Se Jin Im & Masao Hashimoto & Michael Y. Gerner & Junghwa Lee & Haydn T. Kissick & Matheus C. Burger & Qiang Shan & J. Scott Hale & Judong Lee & Tahseen H. Nasti & Arlene H. Sharpe & Gordon J. Freeman, 2016. "Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy," Nature, Nature, vol. 537(7620), pages 417-421, September.
    6. Yannick Simoni & Etienne Becht & Michael Fehlings & Chiew Yee Loh & Si-Lin Koo & Karen Wei Weng Teng & Joe Poh Sheng Yeong & Rahul Nahar & Tong Zhang & Hassen Kared & Kaibo Duan & Nicholas Ang & Micha, 2018. "Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates," Nature, Nature, vol. 557(7706), pages 575-579, May.
    7. Alexander C. Huang & Michael A. Postow & Robert J. Orlowski & Rosemarie Mick & Bertram Bengsch & Sasikanth Manne & Wei Xu & Shannon Harmon & Josephine R. Giles & Brandon Wenz & Matthew Adamow & Debora, 2017. "T-cell invigoration to tumour burden ratio associated with anti-PD-1 response," Nature, Nature, vol. 545(7652), pages 60-65, May.
    8. Ricardo Romero-Moreno & Kimberly J. Curtis & Thomas R. Coughlin & Maria Cristina Miranda-Vergara & Shourik Dutta & Aishwarya Natarajan & Beth A. Facchine & Kristen M. Jackson & Lukas Nystrom & Jun Li , 2019. "The CXCL5/CXCR2 axis is sufficient to promote breast cancer colonization during bone metastasis," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Elaine Lai-Han Leung & Run-Ze Li & Xing-Xing Fan & Lily Yan Wang & Yan Wang & Zebo Jiang & Jumin Huang & Hu-Dan Pan & Yue Fan & Hongmei Xu & Feng Wang & Haopeng Rui & Piu Wong & Hermi Sumatoh & Michae, 2023. "Longitudinal high-dimensional analysis identifies immune features associating with response to anti-PD-1 immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    2. Jani Huuhtanen & Liang Chen & Emmi Jokinen & Henna Kasanen & Tapio Lönnberg & Anna Kreutzman & Katriina Peltola & Micaela Hernberg & Chunlin Wang & Cassian Yee & Harri Lähdesmäki & Mark M. Davis & Sat, 2022. "Evolution and modulation of antigen-specific T cell responses in melanoma patients," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. John P. Finnigan & Jenna H. Newman & Yury Patskovsky & Larysa Patskovska & Andrew S. Ishizuka & Geoffrey M. Lynn & Robert A. Seder & Michelle Krogsgaard & Nina Bhardwaj, 2024. "Structural basis for self-discrimination by neoantigen-specific TCRs," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Meghana Pagadala & Timothy J. Sears & Victoria H. Wu & Eva Pérez-Guijarro & Hyo Kim & Andrea Castro & James V. Talwar & Cristian Gonzalez-Colin & Steven Cao & Benjamin J. Schmiedel & Shervin Goudarzi , 2023. "Germline modifiers of the tumor immune microenvironment implicate drivers of cancer risk and immunotherapy response," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    5. Mike B. Barnkob & Yale S. Michaels & Violaine André & Philip S. Macklin & Uzi Gileadi & Salvatore Valvo & Margarida Rei & Corinna Kulicke & Ji-Li Chen & Vitul Jain & Victoria K. Woodcock & Huw Colin-Y, 2024. "Semaphorin 3A causes immune suppression by inducing cytoskeletal paralysis in tumour-specific CD8+ T cells," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    6. Maria Pia Lenza & Leire Egia-Mendikute & Asier Antoñana-Vildosola & Cátia O. Soares & Helena Coelho & Francisco Corzana & Alexandre Bosch & Prodhi Manisha & Jon Imanol Quintana & Iker Oyenarte & Luca , 2023. "Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    7. Jia Wei & Xiaofeng Lu & Qin Liu & Yao Fu & Song Liu & Yang Zhao & Jiawei Zhou & Hui Chen & Meng Wang & Lin Li & Ju Yang & Fangcen Liu & Liming Zheng & Haitao Yin & Yang Yang & Chong Zhou & Ping Zeng &, 2023. "Neoadjuvant sintilimab in combination with concurrent chemoradiotherapy for locally advanced gastric or gastroesophageal junction adenocarcinoma: a single-arm phase 2 trial," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    8. Irma Telarovic & Carmen S. M. Yong & Lisa Kurz & Irene Vetrugno & Sabrina Reichl & Alba Sanchez Fernandez & Hung-Wei Cheng & Rona Winkler & Matthias Guckenberger & Anja Kipar & Burkhard Ludewig & Mart, 2024. "Delayed tumor-draining lymph node irradiation preserves the efficacy of combined radiotherapy and immune checkpoint blockade in models of metastatic disease," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    9. Ariel Isser & Aliyah B. Silver & Hawley C. Pruitt & Michal Mass & Emma H. Elias & Gohta Aihara & Si-Sim Kang & Niklas Bachmann & Ying-Yu Chen & Elissa K. Leonard & Joan G. Bieler & Worarat Chaisawangw, 2022. "Nanoparticle-based modulation of CD4+ T cell effector and helper functions enhances adoptive immunotherapy," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    10. Xiaofeng Liao & Wenxue Li & Hongyue Zhou & Barani Kumar Rajendran & Ao Li & Jingjing Ren & Yi Luan & David A. Calderwood & Benjamin Turk & Wenwen Tang & Yansheng Liu & Dianqing Wu, 2024. "The CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    11. Jianjiao Ni & Xiaofei Wang & Lin Wu & Xinghao Ai & Qian Chu & Chengbo Han & Xiaorong Dong & Yue Zhou & Yechun Pang & Zhengfei Zhu, 2024. "Sintilimab in combination with stereotactic body radiotherapy and granulocyte-macrophage colony-stimulating factor in metastatic non-small cell lung cancer: The multicenter SWORD phase 2 trial," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    12. Teresa Maria Rosaria Noviello & Anna Maria Giacomo & Francesca Pia Caruso & Alessia Covre & Roberta Mortarini & Giovanni Scala & Maria Claudia Costa & Sandra Coral & Wolf H. Fridman & Catherine Sautès, 2023. "Guadecitabine plus ipilimumab in unresectable melanoma: five-year follow-up and integrated multi-omic analysis in the phase 1b NIBIT-M4 trial," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    13. Ziyang Cao & Dongdong Li & Liang Zhao & Mengting Liu & Pengyue Ma & Yingli Luo & Xianzhu Yang, 2022. "Bioorthogonal in situ assembly of nanomedicines as drug depots for extracellular drug delivery," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    14. Laura Y. Zhou & Fei Zou & Wei Sun, 2023. "Prioritizing candidate peptides for cancer vaccines through predicting peptide presentation by HLA‐I proteins," Biometrics, The International Biometric Society, vol. 79(3), pages 2664-2676, September.
    15. Thomas Thisted & F. Donelson Smith & Arnab Mukherjee & Yuliya Kleschenko & Feng Feng & Zhi-Gang Jiang & Timothy Eitas & Kanam Malhotra & Zuzana Biesova & Adejumoke Onumajuru & Faith Finley & Anokhi Ci, 2024. "VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    16. Zhigui Zuo & Hao Yin & Yu Zhang & Congying Xie & Qinyang Wang, 2023. "A cytotoxic T cell inspired oncolytic nanosystem promotes lytic cell death by lipid peroxidation and elicits antitumor immune responses," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    17. Sanjay M. Prakadan & Christopher A. Alvarez-Breckenridge & Samuel C. Markson & Albert E. Kim & Robert H. Klein & Naema Nayyar & Andrew W. Navia & Benjamin M. Kuter & Kellie E. Kolb & Ivanna Bihun & Jo, 2021. "Genomic and transcriptomic correlates of immunotherapy response within the tumor microenvironment of leptomeningeal metastases," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    18. Judit Svensson-Arvelund & Sara Cuadrado-Castano & Gvantsa Pantsulaia & Kristy Kim & Mark Aleynick & Linda Hammerich & Ranjan Upadhyay & Michael Yellin & Henry Marsh & Daniel Oreper & Suchit Jhunjhunwa, 2022. "Expanding cross-presenting dendritic cells enhances oncolytic virotherapy and is critical for long-term anti-tumor immunity," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    19. Georges Bedran & Daniel A. Polasky & Yi Hsiao & Fengchao Yu & Felipe Veiga Leprevost & Javier A. Alfaro & Marcin Cieslik & Alexey I. Nesvizhskii, 2023. "Unraveling the glycosylated immunopeptidome with HLA-Glyco," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    20. Rana Falahat & Anders Berglund & Patricio Perez-Villarroel & Ryan M. Putney & Imene Hamaidi & Sungjune Kim & Shari Pilon-Thomas & Glen N. Barber & James J. Mulé, 2023. "Epigenetic state determines the in vivo efficacy of STING agonist therapy," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29342-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.