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Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance

Author

Listed:
  • Cirino Botta

    (University of Palermo
    Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), CCUN, Instituto de Investigacion Sanitaria de Navarra (IDISNA), CIBER-ONC numbers CB16/12/00369, CB16/12/00489)

  • Cristina Perez

    (Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), CCUN, Instituto de Investigacion Sanitaria de Navarra (IDISNA), CIBER-ONC numbers CB16/12/00369, CB16/12/00489)

  • Marta Larrayoz

    (Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), CCUN, Instituto de Investigacion Sanitaria de Navarra (IDISNA), CIBER-ONC numbers CB16/12/00369, CB16/12/00489)

  • Noemi Puig

    (Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), CIBER-ONC number CB16/12/00233)

  • Maria-Teresa Cedena

    (Hospital Universitario 12 de Octubre, CIBER-ONC number CB16/12/00369)

  • Rosalinda Termini

    (Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), CCUN, Instituto de Investigacion Sanitaria de Navarra (IDISNA), CIBER-ONC numbers CB16/12/00369, CB16/12/00489)

  • Ibai Goicoechea

    (Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), CCUN, Instituto de Investigacion Sanitaria de Navarra (IDISNA), CIBER-ONC numbers CB16/12/00369, CB16/12/00489)

  • Sara Rodriguez

    (Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), CCUN, Instituto de Investigacion Sanitaria de Navarra (IDISNA), CIBER-ONC numbers CB16/12/00369, CB16/12/00489)

  • Aintzane Zabaleta

    (Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), CCUN, Instituto de Investigacion Sanitaria de Navarra (IDISNA), CIBER-ONC numbers CB16/12/00369, CB16/12/00489)

  • Aitziber Lopez

    (Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), CCUN, Instituto de Investigacion Sanitaria de Navarra (IDISNA), CIBER-ONC numbers CB16/12/00369, CB16/12/00489)

  • Sarai Sarvide

    (Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), CCUN, Instituto de Investigacion Sanitaria de Navarra (IDISNA), CIBER-ONC numbers CB16/12/00369, CB16/12/00489)

  • Laura Blanco

    (Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), CCUN, Instituto de Investigacion Sanitaria de Navarra (IDISNA), CIBER-ONC numbers CB16/12/00369, CB16/12/00489)

  • Daniele M. Papetti

    (University of Milano-Bicocca)

  • Marco S. Nobile

    (Ca’ Foscari University of Venice
    Biostatistics and Bioimaging Centre—B4)

  • Daniela Besozzi

    (University of Milano-Bicocca
    Biostatistics and Bioimaging Centre—B4)

  • Massimo Gentile

    (“Annunziata” Hospital)

  • Pierpaolo Correale

    (Great Metropolitan Hospital “Riuniti” of Reggio Calabria)

  • Sergio Siragusa

    (University of Palermo)

  • Albert Oriol

    (Institut Català d’Oncologia i Institut Josep Carreras)

  • Maria Esther González-Garcia

    (Hospital de Cabueñes)

  • Anna Sureda

    (Institut Català d’Oncologia-Hospitalet, Instituto de Investigación Biomédica de Bellvitge (IDIBELL))

  • Felipe de Arriba

    (Hospital Morales Meseguer, IMIB-Arrixaca, Universidad de Murcia)

  • Rafael Rios Tamayo

    (Hospital Universitario Puerta de Hierro)

  • Jose-Maria Moraleda

    (Hospital Morales Meseguer, IMIB-Arrixaca, Universidad de Murcia)

  • Mercedes Gironella

    (Hospital Vall d’Hebron)

  • Miguel T. Hernandez

    (Hospital Universitario de Canarias)

  • Joan Bargay

    (Hospital Son Llatzer)

  • Luis Palomera

    (Hospital Clínico Lozano Blesa)

  • Albert Pérez-Montaña

    (Hospital Son Espases)

  • Hartmut Goldschmidt

    (University of Heidelberg)

  • Hervé Avet-Loiseau

    (IUC-T Oncopole)

  • Aldo Roccaro

    (ASST Spedali Civili di Brescia)

  • Alberto Orfao

    (CIBER-ONC number CB16/12/00400
    University of Salamanca)

  • Joaquin Martinez-Lopez

    (Hospital Universitario 12 de Octubre, CIBER-ONC number CB16/12/00369)

  • Laura Rosiñol

    (Hospital Clínic IDIBAPS)

  • Juan-José Lahuerta

    (Hospital Universitario 12 de Octubre, CIBER-ONC number CB16/12/00369)

  • Joan Blade

    (Hospital Clínic IDIBAPS)

  • Maria-Victoria Mateos

    (Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), CIBER-ONC number CB16/12/00233)

  • Jesús F. San-Miguel

    (Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), CCUN, Instituto de Investigacion Sanitaria de Navarra (IDISNA), CIBER-ONC numbers CB16/12/00369, CB16/12/00489)

  • Jose-Angel Martinez Climent

    (Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), CCUN, Instituto de Investigacion Sanitaria de Navarra (IDISNA), CIBER-ONC numbers CB16/12/00369, CB16/12/00489)

  • Bruno Paiva

    (Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), CCUN, Instituto de Investigacion Sanitaria de Navarra (IDISNA), CIBER-ONC numbers CB16/12/00369, CB16/12/00489)

Abstract

Tumor recognition by T cells is essential for antitumor immunity. A comprehensive characterization of T cell diversity may be key to understanding the success of immunomodulatory drugs and failure of PD-1 blockade in tumors such as multiple myeloma (MM). Here, we use single-cell RNA and T cell receptor sequencing to characterize bone marrow T cells from healthy adults (n = 4) and patients with precursor (n = 8) and full-blown MM (n = 10). Large T cell clones from patients with MM expressed multiple immune checkpoints, suggesting a potentially dysfunctional phenotype. Dual targeting of PD-1 + LAG3 or PD-1 + TIGIT partially restored their function in mice with MM. We identify phenotypic hallmarks of large intratumoral T cell clones, and demonstrate that the CD27− and CD27+ T cell ratio, measured by flow cytometry, may serve as a surrogate of clonal T cell expansions and an independent prognostic factor in 543 patients with MM treated with lenalidomide-based treatment combinations.

Suggested Citation

  • Cirino Botta & Cristina Perez & Marta Larrayoz & Noemi Puig & Maria-Teresa Cedena & Rosalinda Termini & Ibai Goicoechea & Sara Rodriguez & Aintzane Zabaleta & Aitziber Lopez & Sarai Sarvide & Laura Bl, 2023. "Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41562-6
    DOI: 10.1038/s41467-023-41562-6
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    References listed on IDEAS

    as
    1. 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.
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