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
Cancer Data Science Laboratory, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, USA.
Department of Pathology, Attikon University Hospital, National Kapodistrian University of Athens, Athens, Greece.
Ann Oncol. 2025 Mar;36(3):309-320. doi: 10.1016/j.annonc.2024.11.008. Epub 2024 Nov 17.
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.
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.
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.
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.
免疫疗法改善了一些头颈部鳞状细胞癌（HNSCC）患者的治疗结果。然而，观察到的低且可变的反应率凸显了需要强大的反应生物标志物来选择适合治疗的患者。
我们收集并分析了一个大型HNSCC数据集，该数据集包含11个临床队列，包括1232例患者样本，涵盖多种疾病亚型、免疫检查点阻断（ICB）治疗类型、组织来源、数据模式和测量时间。我们对HNSCC患者血液和肿瘤组织中各种细胞类型、传统生物标志物和新兴预测指标的预测能力进行了全面评估。
肿瘤B细胞浸润成为患者生存和ICB反应的强大且可靠的预测指标。它优于所有其他已确立的ICB反应生物标志物，包括三级淋巴结构特征和众多基于T细胞的特征。B细胞浸润与促进肿瘤根除的“热”抗肿瘤微环境相关。此外，外周血单核细胞（PBMC）中的B细胞水平与肿瘤B细胞水平密切相关，并对ICB反应具有较高的预测价值，在两个独立的临床队列中优势比均较高（≥7.8）。
无论在PBMC还是肿瘤组织中评估，B细胞丰度都是HNSCC中ICB反应最强的预测指标之一。为了转化应用于患者护理，通过细胞计数法测量PBMC中的B细胞丰度为临床决策提供了一种实用且可及的工具。
