TY - JOUR

T1 - Intratumoral T-cell and B-cell receptor architecture associates with distinct immune tumor microenvironment features and clinical outcomes of anti-PD-1/L1 immunotherapy

AU - Schina, Aimilia

AU - Sztupinszki, Zsofia

AU - Marie Svane, Inge

AU - Szallasi, Zoltan

AU - Jönsson, Göran

AU - Donia, Marco

N1 - Publisher Copyright: © 2023 Open Heart

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - B-Lymphocytes

KW - Biomarkers, Tumor

KW - Immune Checkpoint Inhibitors

KW - Receptors, Immunologic

KW - T-Lymphocytes

U2 - 10.1136/jitc-2023-006941

DO - 10.1136/jitc-2023-006941

M3 - Journal article

C2 - 37604641

AN - SCOPUS:85168462104

VL - 11

JO - Journal for ImmunoTherapy of Cancer

JF - Journal for ImmunoTherapy of Cancer

SN - 2051-1426

IS - 8

M1 - 006941

ER -