MST1R as a potential new target antigen of chimeric antigen receptor T cells to treat solid tumors

免疫疗法 嵌合抗原受体 癌症研究 肿瘤微环境 CXCL5型 抗原 CXCL1型 癌症 医学 T细胞 癌症免疫疗法 肺癌 免疫学 趋化因子 肿瘤科 内科学 免疫系统 肿瘤细胞
作者
An Wen,Ju‐Seop Kang,Sukjoong Oh,Ang A. Tu
出处
期刊:The Korean Journal of Physiology and Pharmacology [The Korean Society of Pharmacology]
卷期号:27 (3): 241-256 被引量:8
标识
DOI:10.4196/kjpp.2023.27.3.241
摘要

Although chimeric antigen receptor T cell (CAR-T) is a promising immunotherapy in hematological malignancies, there remain many obstacles to CAR-T cell therapy for solid tumors. Identifying appropriate tumor-associated antigens (TAAs) is especially critical for success. Using a bioinformatics approach, we identified common potential TAAs for CAR-T cell immunotherapy in solid tumors. We used the GEO database as a training dataset to find differentially expressed genes (DEGs) and verified candidates using the TCGA database, obtaining seven common DEGs (HM13, SDC1, MST1R, HMMR, MIF, CD24, and PDIA4). Then, we used MERAV to analyze the expression of six genes in normal tissues to determine the ideal target genes. Finally, we analyzed tumor microenvironment factors. The results of major microenvironment factor analyses showed that MDSCs, CXCL1, CXCL12, CXCL5, CCL2, CCL5, TGF-β, CTLA-4, and IFN-γ were significantly overexpressed in breast cancer. The expression of MST1R was positively correlated with TGF-β, CTLA-4, and IFN-γ. In lung adenocarcinoma, MDSCs, Tregs, CXCL12, CXCL5, CCL2, PD-L1, CTLA-4, and IFN-γ were significantly overexpressed in tumor tissues. The expression of MST1R was positively correlated with TGF-β, CTLA-4, and IFN-γ. In bladder cancer, CXCL12, CCL2, and CXCL5 were significantly overexpressed in tumor tissues. MST1R expression was positively correlated with TGF-β. Our results demonstrate that MST1R has the potential as a new target antigen for treating breast cancer, lung adenocarcinoma, and bladder cancer and may be used as a progression indicator for bladder cancer.
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