Correlation Between NKG2DL Expression and Antitumor Effect of Protein-bound Polysaccharide-K in Tumor-bearing Mouse Models

Ayano Konagai; Kiyoshi Yoshimura; Shouichi Hazama; Noboru Yamamoto; Kazunori Aoki; Tomio Ueno; Masaki Fujioka; Hiroko Iijima; Mariko Kato; Motoyuki Uchida; Tsutomu Wada; Moeko Inoue; Tetsuhiko Asao; Masanori Fuse; Satoshi Wada; Atsuo Kuramasu; Ryoji Kamei; Shigeru Takeda; Shigeru Yamamoto; Shigefumi Yoshino; Masaaki Oka; Hiroaki Nagano

doi:10.21873/anticanres.11796

Correlation Between NKG2DL Expression and Antitumor Effect of Protein-bound Polysaccharide-K in Tumor-bearing Mouse Models

Anticancer Res. 2017 Aug;37(8):4093-4101. doi: 10.21873/anticanres.11796.

Authors

Ayano Konagai^{1

2}, Kiyoshi Yoshimura^{3

4

5}, Shouichi Hazama^{1

6}, Noboru Yamamoto⁴, Kazunori Aoki⁷, Tomio Ueno⁸, Masaki Fujioka², Hiroko Iijima², Mariko Kato², Motoyuki Uchida², Tsutomu Wada², Moeko Inoue⁵, Tetsuhiko Asao⁵, Masanori Fuse⁵, Satoshi Wada⁹, Atsuo Kuramasu¹⁰, Ryoji Kamei¹, Shigeru Takeda¹, Shigeru Yamamoto¹, Shigefumi Yoshino¹, Masaaki Oka¹, Hiroaki Nagano¹

Affiliations

¹ Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
² Pharmaceuticals & Agrochemicals Division, Kureha Corporation, Tokyo, Japan.
³ Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan kiyoshim@ncc.go.jp.
⁴ Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan.
⁵ Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Tokyo, Japan.
⁶ Department of Translational Research and Developmental Therapeutics against Cancer, Yamaguchi University Graduate School of Medicine, Ube, Japan.
⁷ Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
⁸ Department of Digestive Surgery, Kawasaki Medical School, Kurashiki, Japan.
⁹ Division of Cancer Immunotherapy, Kanagawa Cancer Center, Yokohama, Japan.
¹⁰ Department of Molecular Pharmacology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

PMID: 28739693
DOI: 10.21873/anticanres.11796

Abstract

Background/aim: We investigated the relationship between the expression of natural killer group 2, member D ligands (NKG2DLs) and the antitumor effects of protein-bound polysaccharide-K (PSK).

Materials and methods: PSK was administered to evaluate its effectiveness against tumor growth. The expression of Rae-1 and H60 were analyzed in multiple cell lines.

Results: PSK showed the highest antitumor effects in mice implanted with cells expressing neither Rae-1 nor H60. PSK had little antitumor effect in mice implanted with cells expressing both Rae-1 and H60. A correlation between the expression of NKG2DLs and the antitumor effect of PSK was observed. After PSK administration, INF-γ production in CD8⁺ T cells increased in mice with cells expressing neither Rae-1 nor H60, but did not change in mice implanted with cells expressing both Rae-1 and H60.

Conclusion: We demonstrated that the expression of NKG2DLs affects tumor immunity and the efficacy of immuno therapy in tumor-bearing mouse model.

Keywords: H60; NKG2D; NKG2DL; PSK; Rae-1 family.

MeSH terms

Animals
CD8-Positive T-Lymphocytes / drug effects
Cell Line, Tumor
Fungal Proteins / administration & dosage*
Gene Expression Regulation, Neoplastic / drug effects
Humans
Ligands
Mice
Minor Histocompatibility Antigens / biosynthesis
Minor Histocompatibility Antigens / genetics*
NK Cell Lectin-Like Receptor Subfamily K / biosynthesis
NK Cell Lectin-Like Receptor Subfamily K / genetics*
Neoplasms / drug therapy*
Neoplasms / genetics
Neoplasms / pathology
Nuclear Matrix-Associated Proteins / biosynthesis
Nuclear Matrix-Associated Proteins / genetics*
Nucleocytoplasmic Transport Proteins / biosynthesis
Nucleocytoplasmic Transport Proteins / genetics*
Polysaccharides / administration & dosage*
Xenograft Model Antitumor Assays

Substances

Fungal Proteins
KLRK1 protein, human
Ligands
Minor Histocompatibility Antigens
NK Cell Lectin-Like Receptor Subfamily K
Nuclear Matrix-Associated Proteins
Nucleocytoplasmic Transport Proteins
Polysaccharides
RAE1 protein, human
minor H antigen H60
protein-bound polysaccharide K, Basidiomycetes