Supporting data for "Tumor-derived CCL20 drives B cell dysfunction and immunosuppression in nasopharyngeal carcinoma"

The raw data supporting the findings of ‘Tumor-derived CCL20 Drives B Cell Dysfunction and Immunosuppression in Nasopharyngeal Carcinoma’ encompass RNA-sequencing datasets, bioinformatic analyses, flow cytometry, and multiplex immunohistochemistry (mIHC) staining results, among other experimental outputs.Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated malignancy with a B cell-rich microenvironment, the role of tumor factors in shaping B cell immune responses remains poorly understood. Multi-omics analysis of NPC patient specimens revealed that memory B cell infiltration correlates with favorable clinical outcomes. We found that tumor-derived CCL20 drives B cell dysfunction through CCR6-dependent suppression of BCR/AKT signaling, leading to diminished expression of activation markers (CD80/CD86/MHC-II) and impaired memory differentiation via CD27 downregulation. This CCL20-induced "paralyzed" state compromises B cell antigen presentation capacity, resulting in defective CD4+ and CD8+ T cell activation and attenuated cytotoxic responses. Multiplex immunohistochemistry confirmed an inverse relationship between tumor CCL20 levels and both memory B cell frequency and MHC-I expression on CD20+ B cells. Spatial transcriptomic profiling further demonstrated that CCL20-enriched tumor regions colocalize with malignant epithelial cells, exhibit reduced CD4+ T cell infiltration, and display transcriptional suppression of B cell lineage markers (MS4A1/CD20, CD19, CD27, IGHD) and MHC molecules. Collectively, these findings establish that tumor-secreted CCL20 fosters an immunosuppressive niche by paralyzing B cell function, disrupting memory formation, and impairing T cell priming. The CCL20-CCR6 axis represents a therapeutic target to restore antitumor immunity, with CCL20 serving as both a prognostic biomarker and immunotherapeutic intervention point in NPC.

支撑《肿瘤源性CCL20驱动鼻咽癌B细胞功能障碍与免疫抑制》一文研究发现的原始数据涵盖RNA测序（RNA-sequencing）数据集、生物信息学分析、流式细胞术结果以及多重免疫组化（multiplex immunohistochemistry, mIHC）染色结果等多种实验产出。鼻咽癌（Nasopharyngeal Carcinoma, NPC）是一种与EB病毒（Epstein-Barr virus）相关的恶性肿瘤，其肿瘤微环境富含B细胞，但目前学界对肿瘤源性因子如何调控B细胞免疫应答的机制仍知之甚少。对鼻咽癌患者标本的多组学分析显示，记忆性B细胞浸润与良好的临床预后呈正相关。本研究发现，肿瘤源性CCL20可通过CCR6依赖的方式抑制BCR/AKT信号通路，进而驱动B细胞功能障碍：具体表现为B细胞活化标志物（CD80/CD86/MHC-II）表达下调，且通过CD27表达下调损害记忆性B细胞分化过程。这种由CCL20诱导的“瘫痪”状态会削弱B细胞的抗原呈递能力，进而导致CD4+和CD8+ T细胞活化异常，并削弱细胞毒性应答效应。多重免疫组化（mIHC）实验证实，肿瘤组织中CCL20的表达水平与记忆性B细胞的浸润频率以及CD20+B细胞表面MHC-I的表达均呈负相关。空间转录组测序分析进一步显示，富含CCL20的肿瘤区域与恶性上皮细胞共定位，且该区域CD4+ T细胞浸润减少，同时B细胞谱系标志物（MS4A1/CD20、CD19、CD27、IGHD）及MHC分子的转录水平均受到抑制。综上，本研究结果证实，肿瘤分泌的CCL20可通过瘫痪B细胞功能、破坏记忆性B细胞形成以及损害T细胞启动过程，构建出免疫抑制性肿瘤微环境。CCL20-CCR6信号轴可作为恢复抗肿瘤免疫的治疗靶点，而CCL20在鼻咽癌中同时可作为预后生物标志物与免疫治疗干预靶点。