Tumor and Blood B Cell Abundance Outperforms Established Immune Checkpoint Blockade Response Prediction Signatures in Head and Neck Cancer

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 anti-tumor microenvironment that promotes tumor eradication. Furthermore, B cell levels in 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.