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Mesothelin‑specific T cell cytotoxicity against triple negative breast cancer is enhanced by 40s ribosomal protein subunit 3‑treated self‑differentiated dendritic cells

  • Authors:
    • Niphat Jirapongwattana
    • Suyanee Thongchot
    • Wannasiri Chiraphapphaiboon
    • Thaweesak Chieochansin
    • Doonyapat Sa-Nguanraksa
    • Malee Warnnissorn
    • Peti Thuwajit
    • Pa-Thai Yenchitsomanus
    • Chanitra Thuwajit
  • View Affiliations / Copyright

    Affiliations: Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand, Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE‑CIT), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand, Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
    Copyright: © Jirapongwattana et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 127
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    Published online on: May 25, 2022
       https://doi.org/10.3892/or.2022.8338
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Abstract

Triple negative breast cancer (TNBC) lacks targeted treatment resulting in poor prognosis. Targeting overexpressing mesothelin (MSLN) using MSLN‑specific T cells is an attractive treatment approach and the aim of the present study. The expression of MSLN in human TNBC paraffin sections was analyzed by immunohistochemistry. Lentiviral vector harbored granulocyte‑macrophage colony stimulating factor (GM‑CSF), interleukin‑4 (IL‑4) and MSLN cDNAs was constructed to generate self‑differentiated myeloid‑derived antigen‑presenting‑cells reactive against tumor expressing MSLN dendritic cell (MSLN‑SmartDC) for MSLN‑specific T cell activation. The results showed high MSLN in 32.8% of all breast cancer subtypes and 57% in TNBC. High MSLN was significantly associated with TNBC subtype and the absence of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. MSLN‑SmartDC exhibited comparable phenotype to DC generated by exogenous cytokine treatment and an addition of 40s ribosomal protein subunit 3 (RPS3), a toll‑like receptor 4 ligand, enhanced DC maturation and function by upregulation of CD40, CD80 and CD83 expressions and IL‑12p70 secretion. MSLN‑specific CD8+CD69+ IFN‑γ+ T cells were detected in T cells activated by both MSLN‑SmartDC and RPS3‑MSLN‑SmartDC. MSLN‑specific T cells activated by these DCs showed more specific killing capability against naturally expressed MSLN‑HCC70 and artificially MSLN‑overexpressing MDA‑MB‑231 compared with parental MDA‑MB‑231 in both two dimensional (2D)‑ and 3D‑culture systems. In conclusion, the results demonstrated the efficacy of MSLN‑SmartDC to promote MSLN‑specific T cells response against TNBC and RPS3 can enhance the cytolytic activity of these T cells providing an alternative treatment approach for patients with TNBC.
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Copy and paste a formatted citation
Spandidos Publications style
Jirapongwattana N, Thongchot S, Chiraphapphaiboon W, Chieochansin T, Sa-Nguanraksa D, Warnnissorn M, Thuwajit P, Yenchitsomanus P and Thuwajit C: Mesothelin‑specific T cell cytotoxicity against triple negative breast cancer is enhanced by 40s ribosomal protein subunit 3‑treated self‑differentiated dendritic cells. Oncol Rep 48: 127, 2022.
APA
Jirapongwattana, N., Thongchot, S., Chiraphapphaiboon, W., Chieochansin, T., Sa-Nguanraksa, D., Warnnissorn, M. ... Thuwajit, C. (2022). Mesothelin‑specific T cell cytotoxicity against triple negative breast cancer is enhanced by 40s ribosomal protein subunit 3‑treated self‑differentiated dendritic cells. Oncology Reports, 48, 127. https://doi.org/10.3892/or.2022.8338
MLA
Jirapongwattana, N., Thongchot, S., Chiraphapphaiboon, W., Chieochansin, T., Sa-Nguanraksa, D., Warnnissorn, M., Thuwajit, P., Yenchitsomanus, P., Thuwajit, C."Mesothelin‑specific T cell cytotoxicity against triple negative breast cancer is enhanced by 40s ribosomal protein subunit 3‑treated self‑differentiated dendritic cells". Oncology Reports 48.1 (2022): 127.
Chicago
Jirapongwattana, N., Thongchot, S., Chiraphapphaiboon, W., Chieochansin, T., Sa-Nguanraksa, D., Warnnissorn, M., Thuwajit, P., Yenchitsomanus, P., Thuwajit, C."Mesothelin‑specific T cell cytotoxicity against triple negative breast cancer is enhanced by 40s ribosomal protein subunit 3‑treated self‑differentiated dendritic cells". Oncology Reports 48, no. 1 (2022): 127. https://doi.org/10.3892/or.2022.8338
Copy and paste a formatted citation
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Spandidos Publications style
Jirapongwattana N, Thongchot S, Chiraphapphaiboon W, Chieochansin T, Sa-Nguanraksa D, Warnnissorn M, Thuwajit P, Yenchitsomanus P and Thuwajit C: Mesothelin‑specific T cell cytotoxicity against triple negative breast cancer is enhanced by 40s ribosomal protein subunit 3‑treated self‑differentiated dendritic cells. Oncol Rep 48: 127, 2022.
APA
Jirapongwattana, N., Thongchot, S., Chiraphapphaiboon, W., Chieochansin, T., Sa-Nguanraksa, D., Warnnissorn, M. ... Thuwajit, C. (2022). Mesothelin‑specific T cell cytotoxicity against triple negative breast cancer is enhanced by 40s ribosomal protein subunit 3‑treated self‑differentiated dendritic cells. Oncology Reports, 48, 127. https://doi.org/10.3892/or.2022.8338
MLA
Jirapongwattana, N., Thongchot, S., Chiraphapphaiboon, W., Chieochansin, T., Sa-Nguanraksa, D., Warnnissorn, M., Thuwajit, P., Yenchitsomanus, P., Thuwajit, C."Mesothelin‑specific T cell cytotoxicity against triple negative breast cancer is enhanced by 40s ribosomal protein subunit 3‑treated self‑differentiated dendritic cells". Oncology Reports 48.1 (2022): 127.
Chicago
Jirapongwattana, N., Thongchot, S., Chiraphapphaiboon, W., Chieochansin, T., Sa-Nguanraksa, D., Warnnissorn, M., Thuwajit, P., Yenchitsomanus, P., Thuwajit, C."Mesothelin‑specific T cell cytotoxicity against triple negative breast cancer is enhanced by 40s ribosomal protein subunit 3‑treated self‑differentiated dendritic cells". Oncology Reports 48, no. 1 (2022): 127. https://doi.org/10.3892/or.2022.8338
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