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Decitabine facilitates immune recognition of sarcoma cells by upregulating CT antigens, MHC molecules, and ICAM-1

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Tumor Biology

Abstract

Rhabdomyosarcoma, osteosarcoma, and Ewing’s sarcoma are the most common types of sarcoma in children. Despite standard therapy, nearly one third of the patients with Ewing’s sarcoma relapse, and there are limited options with curative potential. Immunotherapy is a promising approach as it can target tumor-specific antigens that are specifically expressed on tumors while sparing non-malignant cells. We have demonstrated that a demethylating chemotherapeutic drug, 5-aza-2’-deoxycytidine (decitabine, DAC) can upregulate the expression of cancer-testis (CT) antigens, MHC molecules, and intracellular cell adhesion molecule-1 on pediatric sarcoma cell lines, resulting in enhanced killing of tumor cells by CT antigen-specific cytotoxic T lymphocytes derived from pediatric sarcoma patients. A significant increase in the mRNA expression levels of MAGE-A1 and MAGE-A3 were found in 70 %, and NY-ESO-1 in 80 % of the sarcoma lines following exposure to pharmacological levels of DAC. The high expression levels of MAGE-A1, MAGE-A3, and NY-ESO-1 were sustained in sarcoma lines and primary tumor lines over 30 days after the cessation of DAC. Furthermore, DAC treatment induced upregulation of MAGE-A1, MAGE-A3, or NY-ESO-1 protein expression in seven of nine lines studied. These studies show that demethylating chemotherapy could be combined with CT antigen-directed immunotherapy for treating pediatric sarcoma.

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Acknowledgment

This work was supported by funds from Solving Kids’ Cancer.

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Authors and Affiliations

  1. Department of Pediatrics, Division of Hematology / Oncology, University of Louisville, Baxter 1, Room 204B, 570 South Preston Street, Louisville, KY, 40202, USA

    Deepa Kolaseri Krishnadas, Fanqi Bai, Satheesh Cheeyancheri Chencheri & Kenneth Lucas

  2. Department of Pediatrics, Division of Hematology / Oncology, Penn State Hershey Children’s Hospital, Hershey, PA, USA

    Lei Bao

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  1. Deepa Kolaseri Krishnadas
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  2. Lei Bao
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Correspondence to Deepa Kolaseri Krishnadas.

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Deepa Kolaseri Krishnadas and Lei Bao contributed equally to this work.

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Krishnadas, D.K., Bao, L., Bai, F. et al. Decitabine facilitates immune recognition of sarcoma cells by upregulating CT antigens, MHC molecules, and ICAM-1. Tumor Biol. 35, 5753–5762 (2014). https://doi.org/10.1007/s13277-014-1764-9

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