肿瘤细胞治疗研究
英文原题：Single-cell transcriptome analysis reveals functional changes in tumour-infiltrating B lymphocytes after chemotherapy in oesophageal squamous cell carcinoma.
我们的发现为化疗期间TIL-B的异质性提供了新的见解，并将有助于理解TIL-B的临床重要性。
肿瘤免疫微环境与癌变及免疫治疗疗效相关。B细胞在体液免疫中发挥主要作用，但肿瘤浸润B淋巴细胞（TIL-Bs）的具体功能尚不清楚。因此，我们的目的是研究食管鳞状细胞癌（ESCC）及淋巴结（LNs）中TIL-Bs在化疗期间的功能异质性。
对23例样本进行了单细胞转录组分析。我们还对166例ESCC样本进行了免疫球蛋白C（IGKC）的免疫组化分析，IGKC是一种抗体分泌细胞（ASC）标志物，并评估了IGKC在2年无复发生存期（RFS）和3年总生存期（OS）中的意义。
共81,246个细胞被分为24个簇。我们基于经典标志物提取B细胞簇，并在ESCC中鉴定出12种TIL-B亚型。我们发现，化疗后TIL-B中协同刺激和CD40信号等多个功能增强。化疗后naive B细胞（NBC）比例下降，NBC中B细胞活化基因上调。肿瘤中ASC比例增加，同时ASC迁移能力丧失，化疗后ASC的抗体产生受到促进。化疗后ASC中上调的差异表达基因与食管癌生存期延长相关（p = .028）。在转移性LN中，ASC比例增加，B细胞分化增强。在免疫组化分析中，高IGKC表达病例的RFS和OS显著优于低IGKC表达病例（RFS：p < .0001，OS：p < .0001）。在多变量分析中，IGKC表达是ESCC中RFS（风险比（HR）：0.23，95%置信区间（CI）：0.12-0.45，p < .0001）和OS（HR：0.20，95% CI：0.086-0.47，p = .0002）的独立有利预后因素。
BACKGROUND: Tumour immune microenvironment is related with carcinogenesis and efficacy of immunotherapy. B cells play major roles in humoral immunity, but detailed functions of tumour-infiltrating B lymphocytes (TIL-Bs) are unknown. Therefore, our aim was to investigate the functional heterogeneity of TIL-Bs in oesophageal squamous cell carcinoma (ESCC) and lymph nodes (LNs) during chemotherapy. METHODS: Single-cell transcriptome analysis was performed on 23 specimens. We also performed immunohistochemical analysis of immunoglobulin C (IGKC), an antibody-secreting cell (ASC) marker, in 166 ESCC samples and evaluated the implication of IGKC in 2-year recurrence free survival (RFS) and 3-year overall survival (OS). RESULTS: A total of 81,246 cells were grouped into 24 clusters. We extracted B cell clusters based on canonical markers and identified 12 TIL-B subtypes in ESCC. We found that several functions, such as co-stimulation and CD40 signalling, were enhanced in TIL-Bs after chemotherapy. The proportion of naive B cells (NBCs) decreased and B cell activation genes were up-regulated in NBCs after chemotherapy. The proportion of ASCs in tumours increased with the loss of migratory abilities and antibody production in ASCs was promoted after chemotherapy. Differentially expressed genes up-regulated with chemotherapy in ASCs correlated with prolonged survival with oesophageal cancer (p = .028). In a metastatic LN, the ASC proportion increased and B cell differentiation was enhanced. In immunohistochemical analysis, RFS and OS of high IGKC expression cases were significantly better than those of low IGKC expression cases (RFS: p < .0001, OS: p < .0001). And in multivariable analysis, the expression of IGKC was an independent favourable prognostic factor for RFS (hazard ratio (HR): 0.23, 95% confidence interval (CI): 0.12-0.45, p < .0001) and OS (HR: 0.20, 95% CI: 0.086-0.47, p = .0002) in ESCC. CONCLUSIONS: Our findings provide novel insights for the heterogeneity of TIL-Bs during chemotherapy and will be useful to understand the clinical importance of TIL-Bs.
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