Intratumoral T-cell and B-cell receptor architecture associates with distinct immune tumor microenvironment features and clinical outcomes of anti-PD-1/L1 immunotherapy
(2023) In Journal for ImmunoTherapy of Cancer 11(8).- Abstract
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... (More)
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.
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- author
- Schina, Aimilia ; Sztupinszki, Zsofia ; Marie Svane, Inge ; Szallasi, Zoltan ; Jönsson, Göran LU and Donia, Marco
- organization
- publishing date
- 2023-08
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- B-Lymphocytes, Biomarkers, Tumor, Immune Checkpoint Inhibitors, Receptors, Immunologic, T-Lymphocytes
- in
- Journal for ImmunoTherapy of Cancer
- volume
- 11
- issue
- 8
- article number
- 006941
- publisher
- BMJ Publishing Group
- external identifiers
-
- pmid:37604641
- scopus:85168462104
- ISSN
- 2051-1426
- DOI
- 10.1136/jitc-2023-006941
- language
- English
- LU publication?
- yes
- id
- 69722e1a-ee77-4334-9deb-f9cca15e9358
- date added to LUP
- 2023-10-31 13:18:50
- date last changed
- 2024-04-19 03:08:41
@article{69722e1a-ee77-4334-9deb-f9cca15e9358,
abstract = {{<p>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.</p>}},
author = {{Schina, Aimilia and Sztupinszki, Zsofia and Marie Svane, Inge and Szallasi, Zoltan and Jönsson, Göran and Donia, Marco}},
issn = {{2051-1426}},
keywords = {{B-Lymphocytes; Biomarkers, Tumor; Immune Checkpoint Inhibitors; Receptors, Immunologic; T-Lymphocytes}},
language = {{eng}},
number = {{8}},
publisher = {{BMJ Publishing Group}},
series = {{Journal for ImmunoTherapy of Cancer}},
title = {{Intratumoral T-cell and B-cell receptor architecture associates with distinct immune tumor microenvironment features and clinical outcomes of anti-PD-1/L1 immunotherapy}},
url = {{http://dx.doi.org/10.1136/jitc-2023-006941}},
doi = {{10.1136/jitc-2023-006941}},
volume = {{11}},
year = {{2023}},
}