Stem Cell Research Center, Shantou University Medical College, Shantou, 515041, Guangdong Province, China.
Cancer Hospital, Shantou University Medical College, Shantou, 515041, Guangdong Province, China.
J Transl Med. 2023 Oct 10;21(1):710. doi: 10.1186/s12967-023-04409-8.
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.
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.
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).
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.
嵌合抗原受体自然杀伤（CAR-NK）细胞疗法是最有前途的免疫疗法之一。尽管它在血液恶性肿瘤中显示出显著的治疗效果，但在包括食管鳞状细胞癌（ESCC）在内的实体瘤中很少取得成功。主要原因是缺乏特异性细胞表面抗原和复杂的肿瘤微环境。在这里，我们鉴定出 CD22，一种血液恶性肿瘤中众所周知的肿瘤表面标志物，在 ESCC 中表达，可能成为 CAR-NK 细胞治疗的潜在靶点。
从癌症基因组图谱（TCGA）数据库中分析了 13 种临床应用的肿瘤细胞表面抗原在患者中的表达情况。此外，通过 qCPR 检测了 2 种 ESCC 细胞系和 2 名患者样本中的 mRNA 表达。然后根据韦恩图，选择 CD22 进行进一步研究。接下来，通过免疫荧光（IF）检测 ESCC 细胞系中 CD22 的表达，通过免疫组化（IHC）检测 87 例人 ESCC 样本中的 CD22 表达。根据 H 评分结果，分析 CD22 表达与临床参数之间的相关性。作为证明，通过实时细胞分析仪（RTCA）平台对 CD22 靶向 CAR-NK 细胞对 ESCC 细胞系的疗效进行了检测。
KYSE-140 和 KYSE-150 细胞系显示出 CD22 的表面表达。IHC 显示 87 例 ESCC 患者样本中 CD22 的阳性率为 80.46%（70/87）。其中，27.59%（24/87）患者样本中观察到 CD22 的细胞膜表达。通过卡方检验，ESCC 中 CD22 的表达与淋巴结转移有关，而与肿瘤浸润深度和临床分期无关。工程化的 CD22 靶向 CAR-NK 细胞对 ESCC 细胞系表现出抑制生长能力（p<0.0001）。
CD22 是 ESCC 中能够被 CAR-NK 细胞靶向的潜在肿瘤表面抗原。基于表达抗 CD22 CAR 的免疫细胞，可能开发出针对 ESCC 的潜在治疗方法。该研究还表明，CD22 CAR-NK 细胞可用于其他癌症，需要更多的体内实验。
