Single‐cell landscape and clinical outcomes of infiltrating B cells in colorectal cancer
Single‐cell landscape and clinical outcomes of infiltrating B cells in colorectal cancer
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DOI：
10.1111/imm.13568
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发表时间：
2022-08
期刊：
影响因子：
6.4
通讯作者：
Jie Xia;Zhan-tao Xie;G. Niu;Zhou Lu;Zhiqiang Wang;Yun Xing;Jun Ren;Zhiqing Hu;Runqi Hong
中科院分区：
文献类型：
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作者：
Jie Xia;Zhan-tao Xie;G. Niu;Zhou Lu;Zhiqiang Wang;Yun Xing;Jun Ren;Zhiqing Hu;Runqi Hong
B细胞构成结肠直肠癌（CRC）中浸润免疫细胞的主要成分。然而，B细胞的特性及其临床意义仍不清楚。在这项研究中，使用单细胞RNA测序和多色免疫荧光染色实验，我们确定了五种不同的B细胞亚型及其在CRC肿瘤微环境中的标记基因、分布模式和功能特性。同时，我们发现在肿瘤部位的IgG浆细胞的比例高于在邻近的正常粘膜组织。此外，肿瘤组织中产生CXCL 13的CD 8 + T细胞可促进三级淋巴样结构（TLS）B细胞的形成，CCL 28-CCR 10轴是IgG浆细胞从TLS外周迁移至肿瘤间质的关键。最后，我们确定了四种不同的结肠免疫类别（CIC：A-D），并发现TLS内的CD 20 + B细胞在一个免疫炎症或热肿瘤组（CIC D）中富集。这种富含B细胞的群体，其特征在于强抗原呈递、IgG浆细胞积累、微卫星不稳定性高（MSI-H）和高肿瘤突变负荷（TMB-H），特别是免疫抑制特性，可能成为未来免疫治疗的潜在预测生物标志物。此外，在免疫治疗队列中，证实了富集B细胞和TLS的患者获得显著的治疗优势。总之，我们的研究结果提供了详细的景观浸润B细胞及其潜在的临床意义，在CRC。
B cells constitute a major component of infiltrating immune cells in colorectal cancer (CRC). However, the characteristics of B cells and their clinical significance remain unclear. In this study, using single‐cell RNA sequencing and multicolour immunofluorescence staining experiments, we identified five distinct subtypes of B cells with their marker genes, distribution patterns and functional properties in the CRC tumour microenvironment. Meanwhile, we found a higher proportion of IgG plasma cells in tumour sites than that in adjacent normal mucosal tissues. In addition, the CXCL13‐producing CD8+ T cells in the tumour tissues could promote the formation of tertiary lymphoid structure (TLS) B cells, and the CCL28–CCR10 axis is pivotal for IgG plasma cell migration from the periphery of TLSs to the tumour stroma. Finally, we identified four distinct colon immune classes (CICs: A–D) and found that CD20+ B cells within TLSs were enriched in one immune‐inflamed or hot tumour group (CIC D). This B cell‐rich group, which was characterized by strong antigen presentation, IgG plasma cells accumulation, microsatellite instability‐high (MSI‐H) and high tumour mutation burden (TMB‐H), as well as immunosuppressive property in particular, might become a potential predictive biomarker for future immunotherapy. Additionally, in an immunotherapy cohort, patients with the enrichment of B cells and TLSs were demonstrated to obtain significant therapeutic advantages. Together, our findings provide the detailed landscape of infiltrating B cells and their potential clinical significance in CRC.