title: Myeloid-derived suppressor cells enhance the expression of melanoma-associated antigen A4 in a Lewis lung cancer murine model.
abstract: The cancer-testis (CT) family of antigens are expressed in multiple types of malignant neoplasm and are silent in normal tissues, apart from the testis. Immunotherapy targeting CT antigens is a promising therapeutic strategy for treatment of solid tumors. One member of this family, melanoma-associated antigen A4 (MAGE-A4), has been demonstrated to be expressed in melanomas and lung cancer. Patients with tumors expressing the MAGE-A4 antigen exhibit specific cellular and humoral immune responses to the antigen, resulting in a favorable prognosis. Conversely, the expression of MAGE-A4 is associated with poor survival in lung cancer. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells, which are upregulated in the cancer microenvironment. Little is known regarding any potential correlation between the expression of MAGE-A4 antigens and the accumulation of MDSCs. The present study aimed to examine the association between circulating MDSC levels and MAGE-A4 expression in a mouse model of Lewis lung cancer. The expression of MAGE-A4 in tumor cells or tissues was evaluated using western blotting, while the percentage of MDSCs (CD11b+Gr-1+) in the blood was detected by flow cytometry. In addition, the suppressive capacity of MDSCs and the effectiveness of MDSC depletion were assessed in C57BL/6 tumor-bearing mice. MDSCs were demonstrated to upregulate MAGE-A4 expression via the phosphosphorylated-signal transducer and activator of transcription 3705pathway, while depletion of MDSCs decreased the tumor growth rate, prolonged median survival and enhanced the recognition of MAGE-A4 by CD8+T cells. These findings indicated that immunotherapeutic strategies involving induction of cytotoxic T lymphocytes that target MAGE-A4, in combination with MDSC depletion, may be an effective approach to immunotherapy for cancer types with high expression of MAGE-A4.
authors: Department of Immunology, Zibo Vocational Institute, Zibo, Shandong 255314, P.R. China.
authors: Guilan
authors: G
authors: Shi
authors: Department of Immunology, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, P.R. China.
authors: Huiru
authors: H
authors: Wang
authors: Department of Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212000, P.R. China.
authors: Xiufen
authors: X
authors: Zhuang
keywords: immunotherapy; lung cancer; melanoma-associated antigen A4; myeloid-derived suppressor cells; phosphorylated-signal transducer and activator of transcription 3705