Tumor and blood B-cell abundance outperforms established immune checkpoint blockade response prediction signatures in head and neck cancer Journal Article
| Authors: | 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. |
| Article Title: | Tumor and blood B-cell abundance outperforms established immune checkpoint blockade response prediction signatures in head and neck cancer |
| Abstract: | Background: Immunotherapy has improved the outcomes for some patients with head and neck squamous-cell carcinoma (HNSCC). However, the low and variable response rates observed highlight the need for robust response biomarkers to select patients for treatment. Patients and methods: We assembled and analyzed a large HNSCC dataset, encompassing 11 clinical cohorts including 1232 patient samples, spanning a variety of disease subtypes and immune checkpoint blockade (ICB) treatment types, tissue sources, data modalities, and timing of measurements. We conducted a comprehensive evaluation of the predictive power of various cell types, traditional biomarkers, and emerging predictors in both blood and tumor tissues of HNSCC patients. Results: Tumor B-cell infiltration emerged as a strong and robust predictor of both patient survival and ICB response. It outperformed all other established biomarkers of response to ICB, including the tertiary lymphoid structure signature and numerous T-cell-based signatures. B-cell infiltration was associated with a ‘hot’ antitumor microenvironment that promotes tumor eradication. Furthermore, B-cell levels in peripheral blood mononuclear cells (PBMCs) correlated strongly with tumor B-cell levels and demonstrated high predictive value for ICB response, with high odds ratios (≥7.8) in two independent clinical cohorts. Conclusion: B-cell abundance, whether assessed in PBMCs or tumor tissues, is one of the strongest predictors of ICB response in HNSCC. For translation to patient care, measuring B-cell abundance in PBMCs via cytometry offers a practical and accessible tool for clinical decision making. © 2024 |
| Keywords: | cancer survival; protein expression; treatment response; human cell; major clinical study; cancer patient; flow cytometry; biological marker; cohort analysis; odds ratio; tumor biopsy; prediction; b lymphocyte; cancer inhibition; patient care; immunoglobulin heavy chain; immunotherapy; head and neck cancer; lymphocytic infiltration; b cells; predictive value; peripheral lymphocyte; head and neck squamous cell carcinoma; tumor microenvironment; lymphocyte subpopulation; immune checkpoint inhibitor; human; article; tertiary lymphoid structure; rna sequencing; data integration; liquid biopsy; checkpoint inhibitor therapy; treatment response biomarker; tumor b cell infiltration |
| Journal Title: | Annals of Oncology |
| Volume: | 36 |
| Issue: | 3 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2025-03-01 |
| Start Page: | 309 |
| End Page: | 320 |
| Language: | English |
| DOI: | 10.1016/j.annonc.2024.11.008 |
| PUBMED: | 39551185 |
| PROVIDER: | scopus |
| PMCID: | PMC11845298 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: L. G. T. Morris -- Source: Scopus |
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