Intratumoral T-cell and B-cell receptor architecture associates with distinct immune tumor microenvironment features and clinical outcomes of anti-PD-1/L1 immunotherapy

Research output: Contribution to journalJournal articleResearchpeer-review

Documents

  • Fulltext

    Final published version, 2.95 MB, PDF document

  • Aimilia Schina
  • Zsofia Sztupinszki
  • Svane, Inge Marie
  • Zoltan Szallasi
  • Göran Jönsson
  • Marco Donia

Background Effective cooperation between B-cells and T-cells within the tumor microenvironment may lead to the regression of established tumors. B-cells and T-cells can recognize tumor antigens with exquisite specificity via their receptor complexes. Nevertheless, whether a diverse intratumoral B-cells and T-cell receptor (BCR, TCR) repertoire affects the tumor immune microenvironment (TIME) and clinical outcomes in patients treated with immunotherapy is unclear. Methods We extracted information on BCR and TCR repertoire diversity from large clinical datasets and measured the association between immune receptor diversity features, the TIME, and clinical outcomes of patients treated with anti-PD-1/PD-L1 immunotherapy. Results In multiple tumor types, an increasingly diverse TCR repertoire was strongly associated with a highly activated TIME, while BCR diversity was more associated with antibody responses but not with the overall B-cell infiltration nor with measures related to intratumoral CD8+T cell activity. Neither TCR nor BCR diversity was independent prognostic biomarkers of survival across multiple cancer types. However, both TCR and BCR diversity improved the performance of predictive models combined with established biomarkers of response to immunotherapy. Conclusion Overall, these data indicate a currently unexplored immunological role of intratumoral B-cells associated with BCR diversity and antibody responses but independent of classical anticancer T-cells intratumoral activities.

Original languageEnglish
Article number006941
JournalJournal for ImmunoTherapy of Cancer
Volume11
Issue number8
Number of pages12
ISSN2051-1426
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© 2023 Open Heart

    Research areas

  • B-Lymphocytes, Biomarkers, Tumor, Immune Checkpoint Inhibitors, Receptors, Immunologic, T-Lymphocytes

ID: 371196216