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Immunoproteasome expression is associated with better prognosis and response to checkpoint therapies in melanoma

Author

Listed:
  • Shelly Kalaora

    (Weizmann Institute of Science)

  • Joo Sang Lee

    (National Cancer Institute
    Sungkyunkwan University School of Medicine)

  • Eilon Barnea

    (Department of Biology, Technion)

  • Ronen Levy

    (Weizmann Institute of Science)

  • Polina Greenberg

    (Weizmann Institute of Science)

  • Michal Alon

    (Weizmann Institute of Science)

  • Gal Yagel

    (Weizmann Institute of Science)

  • Gitit Bar Eli

    (Weizmann Institute of Science)

  • Roni Oren

    (Weizmann Institute of Science)

  • Aviyah Peri

    (Weizmann Institute of Science)

  • Sushant Patkar

    (National Cancer Institute)

  • Lital Bitton

    (Weizmann Institute of Science)

  • Steven A. Rosenberg

    (National Cancer Institute)

  • Michal Lotem

    (Hadassah Medical School)

  • Yishai Levin

    (Weizmann Institute of Science)

  • Arie Admon

    (Department of Biology, Technion)

  • Eytan Ruppin

    (National Cancer Institute)

  • Yardena Samuels

    (Weizmann Institute of Science)

Abstract

Predicting the outcome of immunotherapy treatment in melanoma patients is challenging. Alterations in genes involved in antigen presentation and the interferon gamma (IFNγ) pathway play an important role in the immune response to tumors. We describe here that the overexpression of PSMB8 and PSMB9, two major components of the immunoproteasome, is predictive of better survival and improved response to immune-checkpoint inhibitors of melanoma patients. We study the mechanism underlying this connection by analyzing the antigenic peptide repertoire of cells that overexpress these subunits using HLA peptidomics. We find a higher response of patient-matched tumor infiltrating lymphocytes against antigens diferentially presented after immunoproteasome overexpression. Importantly, we find that PSMB8 and PSMB9 expression levels are much stronger predictors of melanoma patientsʼ immune response to checkpoint inhibitors than the tumors’ mutational burden. These results suggest that PSMB8 and PSMB9 expression levels can serve as important biomarkers for stratifying melanoma patients for immune-checkpoint treatment.

Suggested Citation

  • Shelly Kalaora & Joo Sang Lee & Eilon Barnea & Ronen Levy & Polina Greenberg & Michal Alon & Gal Yagel & Gitit Bar Eli & Roni Oren & Aviyah Peri & Sushant Patkar & Lital Bitton & Steven A. Rosenberg &, 2020. "Immunoproteasome expression is associated with better prognosis and response to checkpoint therapies in melanoma," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14639-9
    DOI: 10.1038/s41467-020-14639-9
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    Cited by:

    1. Juan Blanco-Heredia & Carla Anjos Souza & Juan L. Trincado & Maria Gonzalez-Cao & Samuel Gonçalves-Ribeiro & Sara Ruiz Gil & Dmytro Pravdyvets & Samandhy Cedeño & Maurizio Callari & Antonio Marra & An, 2024. "Converging and evolving immuno-genomic routes toward immune escape in breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Federica Schiavoni & Pedro Zuazua-Villar & Theodoros I. Roumeliotis & Graeme Benstead-Hume & Mercedes Pardo & Frances M. G. Pearl & Jyoti S. Choudhary & Jessica A. Downs, 2022. "Aneuploidy tolerance caused by BRG1 loss allows chromosome gains and recovery of fitness," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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