GM-CSF Promotes Antitumor Immunity by Inducing Th9 Cell Responses

  • Cancer Immunol Res. 2019 Mar;7(3):498-509. doi: 10.1158/2326-6066.CIR-18-0518.
Il-Kyu Kim  1  2 ,  Choong-Hyun Koh  1 ,  Insu Jeon  2 ,  Kwang-Soo Shin  1 ,  Tae-Seung Kang  2 ,  Eun-Ah Bae  2 ,  Hyungseok Seo  2 ,  Hyun-Ja Ko  3  4 ,  Byung-Seok Kim  5 ,  Yeonseok Chung  5 ,  Chang-Yuil Kang  6  2
Affiliations
  • 1. Laboratory of Immunology, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
  • 2. Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
  • 3. Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea.
  • 4. Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.
  • 5. Laboratory of Immune Regulation, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
  • 6. Laboratory of Immunology, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea. [email protected].
PMID: 30728152 DOI: 10.1158/2326-6066.CIR-18-0518
Abstract

GM-CSF as an Adjuvant has been shown to promote antitumor immunity in mice and humans; however, the underlying mechanism of GM-CSF-induced antitumor immunity remains incompletely understood. In this study, we demonstrate that GM-CSF potentiates the efficacy of Cancer vaccines through IL9-producing Th (Th9) cells. GM-CSF selectively enhanced Th9 cell differentiation by regulating the COX2-PGE2 pathway while inhibiting the differentiation of induced regulatory T (iTreg) cells in vitro and in vivo GM-CSF-activated monocyte-derived dendritic cells converted tumor-specific naïve Th cells into Th9 cells, and delayed tumor growth by inducing antitumor CTLs in an IL9-dependent manner. Our findings reveal a mechanism for the adjuvanticity of GM-CSF and provide a rationale for the use of GM-CSF in Cancer vaccines.

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