Oncotarget

Research Papers: Immunology:

Axl acts as a tumor suppressor by regulating LIGHT expression in T lymphoma

Eun-Hee Lee, Eun-Mi Kim, Kon-Young Ji, A-Reum Park, Ha-Rim Choi, Hwa-Youn Lee, Su-Man Kim, Byung Yeoup Chung, Chul-Hong Park, Hyo Jin Choi, Young-Hyeh Ko, Hyoung-Woo Bai and Hyung-Sik Kang _

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Oncotarget. 2017; 8:20645-20655. https://doi.org/10.18632/oncotarget.15830

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Abstract

Eun-Hee Lee1,*, Eun-Mi Kim2,*, Kon-Young Ji3, A-Reum Park3, Ha-Rim Choi4, Hwa-Youn Lee5, Su-Man Kim3, Byung Yeoup Chung1, Chul-Hong Park1, Hyo Jin Choi1, Young-Hyeh Ko6, Hyoung-Woo Bai1, Hyung-Sik Kang3

1Research Division for Biotechnology, Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Institute (KAERI), Jeongeup-si, Jeollabuk-do 580-185, Republic of Korea

2Predictive Model Research Center, Korea Institute of Toxicology, Yuseong-gu, Daejeon, 34114, Republic of Korea

3School of Biological Sciences and Technology, Chonnam National University, Buk-gu, Gwangju 500-757, Republic of Korea

4Department of Nursing, Nambu University, Gwangsan-gu, Gwangju 506-706, Republic of Korea

5Medical Device Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Dong-gu, Daegu 701-310, Republic of Korea

6Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Republic of Korea

*These authors have contributed equally to this work

Correspondence to:

Hyung-Sik Kang, email: kanghs@jnu.ac.kr

Hyoung-Woo Bai, email: hbai@kaeri.re.kr

Keywords: Axl receptor tyrosine kinase, LIGHT, T lymphoma, anti-tumorigenicity, oncogene, Immunology and Microbiology Section, Immune response, Immunity

Received: November 30, 2016    Accepted: February 01, 2017    Published: March 02, 2017

ABSTRACT

Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers. LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells) is a ligand that induces robust anti-tumor immunity by enhancing the recruitment and activation of effector immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T lymphoma cells that stably overexpressed Axl also showed high expression of LIGHT. When Jurkat-Axl cells were treated with Gas6, a ligand for Axl, LIGHT expression was upregulated through activation of the PI3K/AKT signaling pathway and transcriptional induction by Sp1. The lytic activity of cytotoxic T lymphocytes and natural killer cells was enhanced by EL4-Axl cells. In addition, tumor volume and growth were markedly reduced due to enhanced apoptotic cell death in EL4-Axl tumor-bearing mice as compared to control mice. We also observed upregulated expression of CCL5 and its receptor, CCR5, and enhanced intratumoral infiltration of cytotoxic T lymphocytes and natural killer cells in EL4-Axl-bearing mice as compared to mock controls. These data strongly suggested that Axl exerts novel tumor suppressor effects by inducing upregulation of LIGHT in the tumor microenvironment of T lymphoma.


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