2002 Fiscal Year Annual Research Report

NK細胞によるがん細胞の認識と破壊の分子機構

Research Project

Project/Area Number	13214096
Research Institution	Juntendo University
Principal Investigator	八木田秀雄順天堂大学, 医学部, 助教授 (30182306)
Keywords	NK細胞 / 免疫監視 / 転移 / 腫瘍 / NKT細胞 / IFN-γ / CTL
Research Abstract	1. TRAILに高感受性のマウス腎癌細胞株(R331)とTRAIL抵抗性のFLIP導入株、及び、マウスTRAILに対する中和抗体あるいはTRAIL欠損マウスを用いて、肝NK細胞に発現するTRAILは肝転移抑制の重要な内因性機序であることを示した。また、マウスTRAILに対する中和抗体の投与あるいはTRAIL欠損マウスを用い、TRAILがNK細胞及びIFN-γに依存性の皮下腫瘍の抑制に働くことを示すとともに、TRAILはmethylcholanthreneによる化学発がんやp53欠損による腫瘍の自然発生に対しても抑制的に働き、NK細胞及びIFN-γ依存性の腫瘍免疫監視機構の主要なエフェクター分子であることを示した。さらに、TRAIL欠損マウス由来のT細胞を骨移植モデルに用いることにより、TRAILがgraft-versus-host disease(GVHD)には関与しないが、graft-versus-tumor(GVT)効果に重要である事を示した。 2. NKT細胞を特異的に活性化するα-galactosylceramide(α-GalCer)の抗転移効果は、NKT細胞自身の細胞障害活性によらず、産生されたIFN-γ及びそれによって活性化されたNK細胞から産生されるIFN-γによって担われることを、IFN-γやパーフォリン等の欠損マウス由来のNK細胞及びNKT細胞を用いて示した。さらに、TRAIL非依存性の抗転移機序として、IFN-γ依存性の腫瘍血管新生阻害が関与することを示した。 3. CD27リガンドであるCD70あるいはCD28リガンドであるCD80を発現させたNK感受性腫瘍細胞株(RMA-S)を用い、NK細胞上のCD27あるいはCD28を介した活性化は、IFN-γ産生を介して腫瘍特異的なメモリーT細胞(Th1及びCTL)の誘導に働くことを示した。

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] Seki, N.: "Tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis is an important endogeneous mechanism for resistance to liver metastases in murine renal cancer"Cancer Res.. 63. 207-213 (2003)
[Publications] Takeda, K.: "Involvement of tumor necrosis factor-related apoptosis-inducing ligand in NK cell-mediated and IFN-γ-dependent suppression of subcutaneous tumor grouth"Cell.Immunol.. 214. 194-200 (2002)
[Publications] Takeda, K.: "Critical role for tumor necrosis factor-related apoptosis-inducing ligand in immune surveillance against tumor development"J.Exp.Med.. 195. 171-179 (2002)
[Publications] Cretney, E.: "Increased susceptibility to tumor initiation and metastasis in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) deficient mice"J.Immunol.. 168. 1356-1361 (2002)
[Publications] Schmaltz, C.: "T cells require TRAIL for optimal graft-versus-tumor activity"Nature Med.. 8. 1433-1437 (2002)
[Publications] Smyth, M.J.: "Nature's TRAIL-On a path to cancer immunotherapy"Immunity. 18. 1-6 (2003)
[Publications] Smyth, M.J.: "Sequential production of IFN-γ by NKT cells and NK cells is essential for the anti-metastatic effect of α-galactosylceramide"Blood. 99. 1259-1266 (2002)
[Publications] Hayakawa, Y.: "IFN-γ-mediated inhibition of tumor angiogenesis by natural killer T-cell ligand, α-galactosylceramide"Blood. 100. 1728-1733 (2002)
[Publications] Smyth, M.J.: "NKT cells -Conductors of tumor immunity?"Curr.Opin.Immunol.. 14. 165-171 (2002)
[Publications] Smyth, M.J.: "New aspects of natural-killer-cell surveillance and therapy of cancer"Nature Rev.Cancer. 2. 850-861 (2002)
[Publications] Kelly, J.M.: "Induction of tumor-specific T cell memory by NK cell-midiated tumor rejection."Nature Immunol.. 3. 83-90 (2002)
[Publications] Kelly, J. M.: "A role for IFN-γ in primary and secondary immunity generated by NK cell-sensitive tumor-expressing CD8O in vivo"J.Immunol.. 168. 4472-4479 (2002)

2002 Fiscal Year Annual Research Report

NK細胞によるがん細胞の認識と破壊の分子機構

Principal Investigator

八木田 秀雄 順天堂大学, 医学部, 助教授 (30182306)

Research Products

[Publications] Seki, N.: "Tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis is an important endogeneous mechanism for resistance to liver metastases in murine renal cancer"Cancer Res.. 63. 207-213 (2003)

[Publications] Takeda, K.: "Involvement of tumor necrosis factor-related apoptosis-inducing ligand in NK cell-mediated and IFN-γ-dependent suppression of subcutaneous tumor grouth"Cell.Immunol.. 214. 194-200 (2002)

[Publications] Takeda, K.: "Critical role for tumor necrosis factor-related apoptosis-inducing ligand in immune surveillance against tumor development"J.Exp.Med.. 195. 171-179 (2002)

[Publications] Cretney, E.: "Increased susceptibility to tumor initiation and metastasis in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) deficient mice"J.Immunol.. 168. 1356-1361 (2002)

[Publications] Schmaltz, C.: "T cells require TRAIL for optimal graft-versus-tumor activity"Nature Med.. 8. 1433-1437 (2002)

[Publications] Smyth, M.J.: "Nature's TRAIL-On a path to cancer immunotherapy"Immunity. 18. 1-6 (2003)

[Publications] Smyth, M.J.: "Sequential production of IFN-γ by NKT cells and NK cells is essential for the anti-metastatic effect of α-galactosylceramide"Blood. 99. 1259-1266 (2002)

[Publications] Hayakawa, Y.: "IFN-γ-mediated inhibition of tumor angiogenesis by natural killer T-cell ligand, α-galactosylceramide"Blood. 100. 1728-1733 (2002)

[Publications] Smyth, M.J.: "NKT cells -Conductors of tumor immunity?"Curr.Opin.Immunol.. 14. 165-171 (2002)

[Publications] Smyth, M.J.: "New aspects of natural-killer-cell surveillance and therapy of cancer"Nature Rev.Cancer. 2. 850-861 (2002)

[Publications] Kelly, J.M.: "Induction of tumor-specific T cell memory by NK cell-midiated tumor rejection."Nature Immunol.. 3. 83-90 (2002)

[Publications] Kelly, J. M.: "A role for IFN-γ in primary and secondary immunity generated by NK cell-sensitive tumor-expressing CD8O in vivo"J.Immunol.. 168. 4472-4479 (2002)

八木田秀雄順天堂大学, 医学部, 助教授 (30182306)