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

被引:4
作者
An, Wen [1 ,2 ]
Kang, Ju-Seop [1 ,2 ]
Oh, Sukjoong [3 ]
Tu, Ang [4 ]
机构
[1] Hanyang Univ, Dept Pharmacol, Seoul 04763, South Korea
[2] Hanyang Univ, Clin Pharmacol Lab, Seoul 04763, South Korea
[3] Hanyang Univ, Coll Med, Dept Internal Med, Seoul 04763, South Korea
[4] Xiantao Hosp Tradit Chinese Med, Dept Pharm, Xiantao 433000, Peoples R China
关键词
Adenocarcinoma of lung; Breast neoplasms; Chimeric antigen receptorT cell; RON protein; Urinary bladder neoplasms; THERAPY; RECOGNITION; DOMAIN;
D O I
10.4196/kjpp.2023.27.3.241
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Although chimeric antigen receptor T cell (CAR-T) is a promising im-munotherapy 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 microenviron-ment factor analyses showed that MDSCs, CXCL1, CXCL12, CXCL5, CCL2, CCL5, TGF-(3, CTLA-4, and IFN-gamma were significantly overexpressed in breast cancer. The expression of MST1R was positively correlated with TGF-(3, CTLA-4, and IFN-gamma. In lung adenocar-cinoma, MDSCs, Tregs, CXCL12, CXCL5, CCL2, PD-L1, CTLA-4, and IFN-gamma were signifi-cantly overexpressed in tumor tissues. The expression of MST1R was positively cor-related with TGF-(3, CTLA-4, and IFN-gamma. In bladder cancer, CXCL12, CCL2, and CXCL5 were significantly overexpressed in tumor tissues. MST1R expression was positively correlated with TGF-(3. 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.
引用
收藏
页码:241 / 256
页数:16
相关论文
共 34 条
  • [11] Overview of anti-BCMA CAR-T immunotherapy for multiple myeloma and relapsed/refractory multiple myeloma
    Feng, Deming
    Sun, Jian
    [J]. SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 2020, 92 (02)
  • [12] Novel BCMA-OR-CD38 tandem-dual chimeric antigen receptor T cells robustly control multiple myeloma
    Feng, Yaru
    Liu, Xiuying
    Li, Xiaorui
    Zhou, Yating
    Song, Zhiru
    Zhang, Jing
    Shi, Bingjie
    Wang, Jianxun
    [J]. ONCOIMMUNOLOGY, 2021, 10 (01):
  • [13] Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists
    Huang, Da Wei
    Sherman, Brad T.
    Lempicki, Richard A.
    [J]. NUCLEIC ACIDS RESEARCH, 2009, 37 (01) : 1 - 13
  • [14] Receptor Affinity and Extracellular Domain Modifications Affect Tumor Recognition by ROR1-Specific Chimeric Antigen Receptor T Cells
    Hudecek, Michael
    Lupo-Stanghellini, Maria-Teresa
    Kosasih, Paula L.
    Sommermeyer, Daniel
    Jensen, Michael C.
    Rader, Christoph
    Riddell, Stanley R.
    [J]. CLINICAL CANCER RESEARCH, 2013, 19 (12) : 3153 - 3164
  • [15] Jones Benjamin S, 2014, Front Pharmacol, V5, P254, DOI 10.3389/fphar.2014.00254
  • [16] Redirecting migration of T cells to chemokine secreted from tumors by genetic modification with CXCR2
    Kershaw, MH
    Wang, G
    Westwood, JA
    Pachynski, RK
    Tiffany, HL
    Marincola, FM
    Wang, E
    Young, HA
    Murphy, PM
    Hwu, P
    [J]. HUMAN GENE THERAPY, 2002, 13 (16) : 1971 - 1980
  • [17] Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells
    Kloss, Christopher C.
    Condomines, Maud
    Cartellieri, Marc
    Bachmann, Michael
    Sadelain, Michel
    [J]. NATURE BIOTECHNOLOGY, 2013, 31 (01) : 71 - +
  • [18] CD28 costimulation overcomes transforming growth factor-β-mediated repression of proliferation of redirected human CD4+ and CD8+ T cells in an antitumor cell attack
    Koehler, Heike
    Kofler, David
    Hombach, Andreas
    Abken, Hinrich
    [J]. CANCER RESEARCH, 2007, 67 (05) : 2265 - 2273
  • [19] Checkpoint Inhibitors Augment CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy in Relapsed B-Cell Acute Lymphoblastic Leukemia
    Li, Amanda M.
    Hucks, George E.
    Dinofia, Amanda M.
    Seif, Alix E.
    Teachey, David T.
    Baniewicz, Diane
    Callahan, Colleen
    Fasano, Christina
    McBride, Beth
    Gonzalez, Vanessa
    Nazimuddin, Farzana
    Porter, David L.
    Lacey, Simon F.
    June, Carl H.
    Grupp, Stephan A.
    Maude, Shannon L.
    [J]. BLOOD, 2018, 132
  • [20] Network-based approach to identify prognostic biomarkers for estrogen receptor-positive breast cancer treatment with tamoxifen
    Liu, Rong
    Guo, Cheng-Xian
    Zhou, Hong-Hao
    [J]. CANCER BIOLOGY & THERAPY, 2015, 16 (02) : 317 - 324