Tumor and blood B-cell abundance outperforms established immune checkpoint blockade response prediction signatures in head and neck cancer

Chang, T.-G.; Spathis, A.; Schäffer, A.A.; Gavrielatou, N.; Kuo, F.; Jia, D.; Mukherjee, S.; Sievers, C.; Economopoulou, P.; Anastasiou, M.; Moutafi, M.; Pal, L.R.; Vos, J.; Lee, A.S.; Lam, S.; Zhao, K.; Jiang, P.; Allen, C.T.; Foukas, P.; Gomatou, G.; Altan-Bonnet, G.; Morris, L.G.T.; Psyrri, A.; Ruppin, E.

doi:10.1016/j.annonc.2024.11.008

Annals of Oncology

2024

DOI: 10.1016/j.annonc.2024.11.008

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Tumor and blood B-cell abundance outperforms established immune checkpoint blockade response prediction signatures in head and neck cancer

T.-G. Chang,

A. Spathis,

A.A. Schäffer

et al.

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2024

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Induced B-Cell Receptor Diversity Predicts PD-1 Blockade Immunotherapy Response

Che,

Lee,

Abou-Taleb

et al. 2024

Preprint

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Immune checkpoint inhibitors such as anti-PD-1 antibodies (aPD1) can be effective in treating advanced cancers. However, many patients do not respond and the mechanisms underlying these differences remain incompletely understood. In this study, we profile a cohort of patients with locally-advanced or metastatic basal cell carcinoma undergoing aPD-1 therapy using singlecell RNA sequencing, high-definition spatial transcriptomics in tumors and draining lymph nodes, and spatial immunoreceptor profiling, with long-term clinical follow-up. We find that successful responses to PD-1 inhibition are characterized by an induction of B-cell receptor (BCR) clonal diversity after treatment initiation. These induced BCR clones spatially co-localize with T-cell clones, facilitate their activation, and traffic alongside them between tumor and draining lymph nodes to enhance tumor clearance. Furthermore, we validated aPD1-induced BCR diversity as a predictor of clinical response in a larger cohort of glioblastoma, melanoma, and head and neck squamous cell carcinoma patients, suggesting that this is a generalizable predictor of treatment response across many types of cancers. We discover that pre-treatment tumors harbor a characteristic gene expression signature that portends a higher probability of inducing BCR clonal diversity after aPD-1 therapy, and we develop a machine learning model that predicts PD-1-induced BCR clonal diversity from baseline tumor RNA sequencing. These findings underscore a dynamic role of B cell diversity during immunotherapy, highlighting its importance as a prognostic marker and a potential target for intervention in non-responders.

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Induced B-Cell Receptor Diversity Predicts PD-1 Blockade Immunotherapy Response

Che,

Lee,

Abou-Taleb

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

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Tumor and blood B-cell abundance outperforms established immune checkpoint blockade response prediction signatures in head and neck cancer

Cited by 1 publication

References 57 publications

Induced B-Cell Receptor Diversity Predicts PD-1 Blockade Immunotherapy Response

Induced B-Cell Receptor Diversity Predicts PD-1 Blockade Immunotherapy Response

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