Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Immunol. 2022 May 11;13:865596. doi: 10.3389/fimmu.2022.865596. eCollection 2022.
As the indication for immunotherapy is rapidly expanding, it is crucial to accurately identify patients who are likely to respond. Infiltration of B cells into many tumor types correlates with a good response to immune checkpoint inhibitor (ICI) therapy. However, B cells' roles in the anti-tumor response are far from clear.
Based on single-cell transcriptomic data for ICI-treated patients, we identified a B-cell cluster [B (ICI-Responsive B) cells] and described the phenotype, cell-cell communication, biological processes, gene signature, and prognosis value of B cells through bioinformatic analysis, tissue immunofluorescence, and animal experiments. Surgery samples from 12 non-small cell lung carcinoma (NSCLC) patients with adjuvant checkpoint blockade were evaluated as external validation.
B cells were identified as a subset of CD20CD22ADAM28 B cells with a memory phenotype. Bioinformatic analysis revealed that B cells had enhanced cell viability and epigenetic regulation, and that ALOX5AP, MIF, and PTPRC/CD45 expressed by myeloid cells may be critical coordinators of diverse biological processes of B cells. Immunofluorescence confirmed the presence of B cells in tertiary lymphoid structures (TLSs) in skin SCC, RCC, CRC, and breast cancer. B-associated gene signatures correlate with positive outcomes in patients with melanoma, glioblastoma, NSCLC, HNSCC, or RCC treated with ICI therapy, and B-cell density predicted NSCLC patients' response to checkpoint immunotherapy. In line with this, melanoma-bearing mice depleted of B cells were resistant to ICIs.
CD20CD22ADAM28 B cells were present in cancer-associated TLS and promoted the response to ICI therapy.
随着免疫疗法的适应证迅速扩大，准确识别可能有反应的患者至关重要。许多肿瘤类型中 B 细胞的浸润与免疫检查点抑制剂（ICI）治疗的良好反应相关。然而，B 细胞在抗肿瘤反应中的作用远未明确。
基于接受 ICI 治疗患者的单细胞转录组数据，我们鉴定出一个 B 细胞簇[B（ICI 反应性 B）细胞]，并通过生物信息学分析、组织免疫荧光和动物实验描述了 B 细胞的表型、细胞间通讯、生物学过程、基因特征和预后价值。对 12 例接受辅助检查点阻断治疗的非小细胞肺癌（NSCLC）患者的手术样本进行了评估，作为外部验证。
B 细胞被鉴定为具有记忆表型的 CD20CD22ADAM28 B 细胞亚群。生物信息学分析显示，B 细胞具有增强的细胞活力和表观遗传调控，髓细胞表达的 ALOX5AP、MIF 和 PTPRC/CD45 可能是 B 细胞多种生物学过程的关键协调因子。免疫荧光证实了 B 细胞存在于皮肤 SCC、RCC、CRC 和乳腺癌的三级淋巴结构（TLS）中。B 相关基因特征与接受 ICI 治疗的黑色素瘤、胶质母细胞瘤、NSCLC、头颈部鳞状细胞癌或 RCC 患者的阳性结局相关，B 细胞密度预测了 NSCLC 患者对检查点免疫治疗的反应。与此一致的是，B 细胞耗竭的黑色素瘤小鼠对 ICI 耐药。
CD20CD22ADAM28 B 细胞存在于癌症相关的 TLS 中，并促进了对 ICI 治疗的反应。
