1998 Fiscal Year Annual Research Report

サイトカインによる担癌宿主T細胞の応答制御

Research Project

Project/Area Number	06282234
Research Institution	Osaka University
Principal Investigator	濱岡利之大阪大学, 医学部, 教授 (60028529)
Co-Investigator(Kenkyū-buntansha)	緒方正人大阪大学, 医学部, 助手 (60224094) 小野史郎大阪大学, 医学部, 助教授 (80127208)
Keywords	担癌 / IL-12 / IFN-γ / 浸潤 / 血管内皮細胞 / 接着分子 / CD40L / 抗腫瘍免疫
Research Abstract	担癌宿主にIL-12を投与すると、抗腫瘍T細胞の抑制が解除され、ある種の腫瘍系では腫瘍の完全退縮が誘導できる。IL-12が担癌宿主免疫系に作用して腫瘍を拒絶させる際、腫瘍局所に多数のT細胞の浸潤が認められる。しかしIL-12無効の腫瘍系ではこれが見られない。そこでIL-12がT細胞の腫瘍局所への浸潤能を亢進させることを直接証明する実験系で解析したところ、IL-12は末梢リンパ組織の抗腫瘍性T細胞を活性化し、T細胞に腫瘍局所への浸潤能力を賦与する。この際IL-12により活性化された担癌宿主のT細胞は、VLA-4とVCAM-1,LFA-1とICAM-1の分子間相互作用を介して腫瘍組織の血管内皮細胞と相互作用し腫瘍組織内に浸潤する。また、IL-12奏効性腫瘍系では、腫瘍局所で産生されるlFN-γはT細胞の腫瘍組織への呼び込みに重要な役割を果たす。腫瘍局所で見られる持続的IFN-γ産生の機構に関しては、腫瘍塊内においてIL-12p35,p40mRNAが共にIL-12治療後持続的に誘導されていることがわかった。更にIL-12mRNAの発現と併行して、Mφ/APCのIL-12産生を誘導出来るCD40ligand(CD40L)の持続的mRNAの発現も検出された。このことからIL-12治療により腫瘍塊にT細胞が浸潤すれば、T細胞とMφ/APCの間でpositlve feedback loopを形成してIL-12とIFN-γが持続的に産生されるようになり、それが腫瘍拒絶に至る抗腫瘍効果の発現につながることが示唆された。

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] Ogawa,M.et al.: "A critical role for a peritumoral stromal reaction in the induction of T cell migration responsible for IL-12 induced tumor regression." Cancer Res.(in press).
[Publications] Yashiro,Y.et al.: "A fundamental difference in the capacity to induce proliferation of naive T cells between CD28 and other costimulatory molecules." Eur.J.Immunol.28. 926-935 (1998)
[Publications] Wijesuriya,R.et al.: "B cell-mediated down-regulation of IFN-γ and IL-12 production induced during anti-tumor immune responses in the tumor-bearing state." Int.Immunology. 10. 1057-1065 (1998)
[Publications] Toyo-oka;K.et al.: "A caspase inhibitor protects thymocytes from diverse signal-mediated apoptosis but not from clonal deletion in fetal thymus organ culture." Immunol.Letters. 63. 83-89 (1998)
[Publications] Tomura,M.et al.: "A critical role for interleukin-18 in the proliferation and activation of NK1.1+CD3-cells." J.Immunol.160. 4738-4746 (1998)
[Publications] Tomura,M.et al.: "Differential capacities of CD4+,CD8+ and CD4-CD8-T cell subsets to express IL-18 receptor and produce IFN-γ in response to IL-18." J.Immunol.160. 3759-3765 (1998)
[Publications] Park,C.-S.et al.: "Differential involvement of a Fas-CPP32-like protease pathway in apoptosis of TCR/CD9-costimulated,naive T cells and TCR-restimulated,activated T cells." J.Immunol.160. 5790-5796 (1998)
[Publications] Ogawa,M.et al.: "Multiple roles of IFN-γ in the mediation of IL-12-induced tumor regression." Cancer Research. 58. 2426-2432 (1998)
[Publications] Kosugi,A.et al.: "Physical and functional association between thymic shared antigen-1/shltem cell antigen 2 and the T cell receptor complex." J.Biol.Chem.273. 12301-12306 (1998)
[Publications] Hosaka,Y.et al.: "Ultrastructure of murine tumour cell lines defective in MHC class I expression before and after interferon-γ treatment." J.Electron Microscopy. 47. 495-503 (1998)
[Publications] Fujiwara,H.et al.: "Molecular mechanisms underlying T cell migration responsible for IL-12-induced tumor regression." Gann Monograph in Cancer Reseach. (in press).
[Publications] Ahn,H.-J.et.al.: "Requirement for distinct Janus kinases and STAT proteins in T cell proliferation versus IFN-γ production follwing IL-12 stimulation." J.Immunol.161. 5893-5900 (1998)

1998 Fiscal Year Annual Research Report

サイトカインによる担癌宿主T細胞の応答制御

Principal Investigator

濱岡 利之 大阪大学, 医学部, 教授 (60028529)

Research Products

[Publications] Ogawa,M.et al.: "A critical role for a peritumoral stromal reaction in the induction of T cell migration responsible for IL-12 induced tumor regression." Cancer Res.(in press).

[Publications] Yashiro,Y.et al.: "A fundamental difference in the capacity to induce proliferation of naive T cells between CD28 and other costimulatory molecules." Eur.J.Immunol.28. 926-935 (1998)

[Publications] Wijesuriya,R.et al.: "B cell-mediated down-regulation of IFN-γ and IL-12 production induced during anti-tumor immune responses in the tumor-bearing state." Int.Immunology. 10. 1057-1065 (1998)

[Publications] Toyo-oka;K.et al.: "A caspase inhibitor protects thymocytes from diverse signal-mediated apoptosis but not from clonal deletion in fetal thymus organ culture." Immunol.Letters. 63. 83-89 (1998)

[Publications] Tomura,M.et al.: "A critical role for interleukin-18 in the proliferation and activation of NK1.1+CD3-cells." J.Immunol.160. 4738-4746 (1998)

[Publications] Tomura,M.et al.: "Differential capacities of CD4+,CD8+ and CD4-CD8-T cell subsets to express IL-18 receptor and produce IFN-γ in response to IL-18." J.Immunol.160. 3759-3765 (1998)

[Publications] Park,C.-S.et al.: "Differential involvement of a Fas-CPP32-like protease pathway in apoptosis of TCR/CD9-costimulated,naive T cells and TCR-restimulated,activated T cells." J.Immunol.160. 5790-5796 (1998)

[Publications] Ogawa,M.et al.: "Multiple roles of IFN-γ in the mediation of IL-12-induced tumor regression." Cancer Research. 58. 2426-2432 (1998)

[Publications] Kosugi,A.et al.: "Physical and functional association between thymic shared antigen-1/shltem cell antigen 2 and the T cell receptor complex." J.Biol.Chem.273. 12301-12306 (1998)

[Publications] Hosaka,Y.et al.: "Ultrastructure of murine tumour cell lines defective in MHC class I expression before and after interferon-γ treatment." J.Electron Microscopy. 47. 495-503 (1998)

[Publications] Fujiwara,H.et al.: "Molecular mechanisms underlying T cell migration responsible for IL-12-induced tumor regression." Gann Monograph in Cancer Reseach. (in press).

[Publications] Ahn,H.-J.et.al.: "Requirement for distinct Janus kinases and STAT proteins in T cell proliferation versus IFN-γ production follwing IL-12 stimulation." J.Immunol.161. 5893-5900 (1998)

濱岡利之大阪大学, 医学部, 教授 (60028529)