肿瘤细胞治疗研究
英文原题：CD22 is a potential target of CAR-NK cell therapy for esophageal squamous cell carcinoma.
CD22 是 ESCC 中可被 CAR-NK 细胞靶向的潜在肿瘤表面抗原。
背景：嵌合抗原受体自然杀伤（CAR-NK）细胞疗法是最有前景的免疫疗法之一。尽管其治疗血液系统恶性肿瘤已取得显著效果，在食管鳞状细胞癌（ESCC）等实体瘤中成功案例仍较少，主要原因是缺少特异性细胞表面抗原以及肿瘤微环境复杂。本研究发现，血液系统恶性肿瘤中已知的肿瘤表面标志物CD22也表达于ESCC，可能成为CAR-NK治疗的潜在靶点。方法：研究分析癌症基因组图谱（TCGA）数据库中患者的13种临床使用肿瘤细胞表面抗原表达，并采用qPCR检测两种ESCC细胞系及两份患者样本中的mRNA表达。随后根据维恩图分析选择CD22进一步研究，分别通过免疫荧光检测ESCC细胞系CD22表达，通过免疫组化检测87例人ESCC样本CD22表达。依据H评分分析CD22表达与临床参数的相关性，并使用实时细胞分析仪（RTCA）平台验证CD22靶向CAR-NK细胞对ESCC细胞系的疗效。结果：KYSE-140和KYSE-150细胞系表面均表达CD22。免疫组化显示，ESCC患者样本中CD22阳性率为80.46%（70/87），其中27.59%（24/87）患者样本可见细胞膜CD22表达。卡方检验显示，ESCC中CD22表达与淋巴结转移相关，但与肿瘤浸润深度和临床分期无关。工程化CD22靶向CAR-NK细胞可抑制ESCC细胞系生长（p<0.0001）。结论：CD22是ESCC中可由CAR-NK细胞靶向的潜在肿瘤表面抗原。以表达抗CD22 CAR的免疫细胞为基础，有望开发ESCC疗法；CD22 CAR-NK也可能用于其他癌症，但仍需开展更多体内实验。
BACKGROUND: Chimeric antigen receptor NK (CAR-NK) cell therapy is one of the most promising immunotherapies. Although it has shown a significant therapeutic effect in hematologic malignancies, few successes have been obtained in solid tumors including esophageal squamous cell carcinoma (ESCC). The major reasons are lack of specific cell surface antigens and complex tumor microenvironment. Here we identify CD22, a well-known tumor surface marker in hematologic malignancies, is expressed in ESCC, possibly serving as a potential target of CAR-NK cell therapy. METHODS: The expression of 13 tumor cell surface antigens used clinically was analyzed in patients from The Cancer Genome Atlas (TCGA) database. Also, mRNA expression were detected in 2 ESCC cell lines and 2 patients samples by qCPR. Then according to Venn diagram, CD22 was selected for further investigation. Following this, the expression of CD22 by immunofluorescence (IF) in ESCC cell lines and by immunohistochemistry (IHC) in 87 cases of human ESCC samples was detected respectively. On the basis of H-score results, the correlation between CD22 expression and clinical parameters was analyzed. As a proof, the efficacy of CD22-targeted CAR-NK cells against ESCC cell lines was performed by a real-time cell analyzer (RTCA) platform. RESULTS: KYSE-140 and KYSE-150 cell lines displayed surface expression of CD22. IHC showed an 80.46% (70/87) positive rate in ESCC patient samples. Among these, cell membranous expression of CD22 was observed in 27.59% (24/87) patient samples. Through chi-square test, expression of CD22 in ESCC was associated with lymph node metastasis while it was no related to the depth of tumor invasion and clinical stage. Engineered CD22-targeted CAR-NK cells exhibited inhibitory growth capability against ESCC cell lines (p < 0.0001). CONCLUSIONS: CD22 is a potential tumor surface antigen capable of being targeted by CAR-NK cells in ESCC. And potential therapeutics for ESCC may be developed based on immune cells expressing anti-CD22 CAR. The study also indicates that CD22 CAR-NK cells could be used in other cancers and more in vivo experiments are needed.
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