Intratumoral T-cell and B-cell receptor architecture associates with distinct immune tumor microenvironment features and clinical outcomes of anti-PD-1/L1 immunotherapy
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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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 006941 |
| Tidsskrift | Journal for ImmunoTherapy of Cancer |
| Vol/bind | 11 |
| Udgave nummer | 8 |
| Antal sider | 12 |
| ISSN | 2051-1426 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
The authors would like to acknowledge the TCGA Research Network as well as the authors who made their clinical datasets available in public repositories, such as the Sequence Read Archive (GSE78220 and GSE91061), the European Nucleotide Archive (PRJEB23709 and PRJEB25780), the database of Genotypes and Phenotype (phs000452.V.3.p1, phs001493.V.1.p1, and phs001919.V.1.p1), and the European Genome-phenome Archive (EGAS00001002928, EGAS00001002556, EGAS00001004445), and their respective respecting funding agencies. Therefore, this study was also supported by the National Human Genome Research Institute (NHGRI) Large Scale Sequencing Program, Grant U54 HG003067 to the Broad Institute (PI, Lander); an AACR KureIt grant (PI, Van Allen, Dana-Farber Cancer Institute, Boston, Massachusetts, USA, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA); Antoni Ribas MD, PhD University of California, Los Angeles, Funding Source:R35 CA197633 National Institutes of Health, Bethesda, Maryland, USA. Miklos Diossy, Ph.D. (Technical University of Denmark, Lyngby, Denmark) is acknowledged for providing valuable scientific insights. The authors would finally like to thank the Computerome 2.0 HPC Facility for hosting and 413 storing data and providing analysis tools that were widely used in this study.
Funding Information:
The study was sponsored by the Danish National Board of Health grant numbers 05-0400-18 and 05- 0400-50, 'Empowering Cancer Immunotherapy in Denmark', the Herlev and Gentofte Hospital Research Council under Clinician-Scientist Grant, and the Lundbeck Foundation under Grant R307-2018-3636. According to the use of clinical datasets available in dbGaP repositories, this study was also supported by the National Human Genome Research Institute (NHGRI) Large Scale Sequencing Program, Grant U54 HG003067 to the Broad Institute (PI, Lander); an AACR KureIt grant (PI, Van Allen, Dana-Farber Cancer Institute, Boston, MA, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA); Antoni Ribas MD, PhD University of California, Los Angeles, Funding Source:R35 CA197633 National Institutes of Health, Bethesda, Maryland, USA.
Funding Information:
The authors would like to acknowledge the TCGA Research Network as well as the authors who made their clinical datasets available in public repositories, such as the Sequence Read Archive (GSE78220 and GSE91061), the European Nucleotide Archive (PRJEB23709 and PRJEB25780), the database of Genotypes and Phenotype (phs000452.V.3.p1, phs001493.V.1.p1, and phs001919.V.1.p1), and the European Genome-phenome Archive (EGAS00001002928, EGAS00001002556, EGAS00001004445), and their respective respecting funding agencies. Therefore, this study was also supported by the National Human Genome Research Institute (NHGRI) Large Scale Sequencing Program, Grant U54 HG003067 to the Broad Institute (PI, Lander); an AACR KureIt grant (PI, Van Allen, Dana-Farber Cancer Institute, Boston, Massachusetts, USA, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA); Antoni Ribas MD, PhD University of California, Los Angeles, Funding Source:R35 CA197633 National Institutes of Health, Bethesda, Maryland, USA. Miklos Diossy, Ph.D. (Technical University of Denmark, Lyngby, Denmark) is acknowledged for providing valuable scientific insights. The authors would finally like to thank the Computerome 2.0 HPC Facility for hosting and 413 storing data and providing analysis tools that were widely used in this study.
Publisher Copyright:
© 2023 Open Heart
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