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

Schina, Aimilia (author)
Copenhagen University Hospital
Sztupinszki, Zsofia (author)
Danish Cancer Society
Marie Svane, Inge (author)
Copenhagen University Hospital
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Szallasi, Zoltan (author)
Danish Cancer Society
Jönsson, Göran (author)
Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
Donia, Marco (author)
Copenhagen University Hospital
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 (creator_code:org_t)
2023
2023
English.
In: Journal for ImmunoTherapy of Cancer. - 2051-1426. ; 11:8
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Keyword

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

Publication and Content Type

art (subject category)
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