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書籍詳細

未契約
書籍名 腫瘍免疫学
出版社 癌と化学療法社
発行日 2010-09-24
著者
  • 折田薫三(著)
ISBN 9784906225446
ページ数 268
版刷巻号 初版第1刷
分野
閲覧制限 未契約

急速に膨張しつつある腫瘍免疫の今日的な知識と理解を学ぶための格好の教科書である。

目次

  • 表紙
  • 推薦のことば
  • はじめに
  • 目次
  • A. 総論 Cancer immunoediting
    • I. Elimination
    • II. Equilibrium
    • III. Escape
  • B. 腫瘍細胞の微小環境下での免疫逃避
    • I. 腫瘍内浸潤リンパ球(tumor-infiltrating lymphocyte, TIL)のanergy, dysfunction
    • II. 腫瘍細胞側の免疫逃避機構
      • 1. 腫瘍細胞の表面抗原の低下, 消失, 変化
        • 1) MHCクラスI分子
        • 2) 腫瘍関連抗原(tumor-associated antigen, TAA)
        • 3) Antigen processing machinery (APM) 機構(内在性抗原processing機構)の異常
        • 4) MHCクラスII分子
        • 5) Human leukocyte antigen G(HLA-G)分子
        • 6) Human leukocyte antigen E(HLA-E)分子
        • 7) Forkhead box 3(Foxp3)
        • 8) Glucocorticoid-induced TNF-receptor ligand(GITRL)
        • 9) Immunoglobulin-like transcript(ILT)-3, ILT-4
      • 2. 免疫阻害分子
        • 1) Indoleamine 2,3-dioxygenase(IDO)
        • 2) Arginase(ARG)とnitric oxide synthase(NOS)
        • 3) 可溶性NKG2D ligand
        • 4) 可溶性GITR ligand(GITRL)
        • 5) Ganglioside(GD)
        • 6) Galectin
        • 7) Fas tumor counterattack
        • 8) CD200(OX2)
      • 3. 共刺激阻止リガンド(coinhibitory ligand)の発現
        • 1) B7-H1(programmed death ligand 1, PD-L1)
        • 2) B7-H2(ICOS-L)
        • 3) B7-H3
        • 4) B7-H4
      • 4. 免疫抑制性サイトカイン, ケモカイン, cyclooxygenase 2(COX-2)/prostaglandin E2(PGE2)
        • 1) IL-10
        • 2) TGF-β
          • a. TGF-βシグナルの阻止
            • a) 抗TGF-β抗体
            • b) TGF-βRI(TβRI)kinase阻害剤
            • c) TGF-β antisense
            • d) TGF-β siRNA
        • 3) Cyclooxygenase 2(COX-2)/prostaglandin E2(PGE2)
        • 4) Vascular endothelial growth factor(VEGF)
        • 5) Macrophage migration inhibitory factor(MIF)
    • III. 宿主側の免疫逃避機構
      • 1. 免疫抑制性T細胞の集積, 誘導, 増殖
        • 1) CD4+CD25+regulatory T細胞(CD4+Treg細胞, Treg細胞)
        • 2) Type 1 regulatory T(Tr1)細胞
        • 3) IL-10+CCR7+CD8+Treg細胞
        • 4) IL-10+CD8+D28-Treg細胞
        • 5) CD8+CD25+Foxp3+Treg細胞
        • 6) Heme oxygenase-1(HO-1)特異的CD8+CD25-Foxp3-Treg細胞
        • 7) γδT細胞
        • 8) NKT細胞
      • 2. Myeloid-derived suppressor cell(MDSC)
        • 1) Tumor-derived factor(TDF)によるMDSCの誘導
        • 2) MDSCの免疫抑制機作
          • a. TGF-β
          • b. Arginase(ARG)
          • c. Nitoric oxide synthase(NOS)
          • d. Reactive oxygen species(ROS)
          • e. Peroxynitrite(ONOO-)
          • f. Treg細胞の誘導
          • g. その他の抑制作用
          • h. ヒトMDSCの免疫抑制
        • 3) MDSCと免疫抑制細胞とのネットワーク
          • a. TAMとのクロストーク
          • b. NKT細胞とのクロストーク
          • c. Treg細胞とのクロストーク
        • 4) MDSCの免疫抑制能の解除
          • a. In vivoでのMDSCの除去
          • b. MDSCの分化・促進
          • c. MDSCの抑制経路のブロック
          • d. STAT3などの抑制
          • e. Peroxisome proliferator-activated receptor γ(PPARγ)刺激, phospholipase A2(PLA2)抑制
      • 3. 腫瘍関連Mφ(tumor-associated Mφ, TAM)
        • 1) M1-M2パラダイム
        • 2) TAM
          • a. TAMのorigin
          • b. TAMの免疫抑制機作
            • a) ROSによるCD3ζの欠損
            • b) B7-H4の発現
            • c) 可溶性ILT-3の産生
      • 4. MDSCとTAMの関係
      • 5. 腫瘍内浸潤DC(tumor-infiltrating DC, TID)
      • 6. 腫瘍関連fibroblast(tumor-associated fibroblast, TAF)
        • 1) TAF由来の物質とextracellular matrix(ECM)成分の反応による免疫抑制
          • a. Tenasin
          • b. Thrombospondin-1(TSP-1)
        • 2) TAF由来のサイトカイン, ケモカイン
        • 3) B7-H1(PD-L1), B7-DC(PD-L2)の発現
  • C. 手術と免疫
    P.67閲覧
    • I. 手術侵襲と細胞性免疫
    • II. 腫瘍切除に伴う免疫逃避の解除
  • D. 免疫療法
    P.76閲覧
    • I. 免疫非修飾癌患者に対する腫瘍ワクチン療法
      • 1. 進行癌に対する治療的腫瘍ワクチン療法
      • 2. 手術後の補助的腫瘍ワクチン療法
      • 3. 腫瘍vaccination適応患者の選択
    • II. 免疫修飾担癌宿主に対する腫瘍ワクチン療法
      • 1. CD4+Treg細胞除去と腫瘍ワクチン療法
        • 1) 抗CD25抗体
        • 2) 抗CTLA-4抗体
        • 3) Agonistic抗GITR抗体
        • 4) Agonistic抗OX40(CD134)抗体
        • 5) Foxp3特異的CTLの誘導
        • 6) 化学療法(cyclophosphamide, CPA)
        • 7) Treg細胞を特異的に抑制する薬剤
          • a. Tumor necrosis factor(TNF)
          • b. Imatinib mesylate
          • c. Sunitinib
          • d. その他
      • 2. MDSC除去と腫瘍ワクチン療法
        • 1) Gemcitabine(GEM)
        • 2) Sunitinib
    • III. T細胞養子移入療法(adoptive T cell transfer, ACT)
      • 1. TAA特異的central memory CD8+T細胞の誘導(in vitro)
      • 2. Lymphodepleting宿主へのadoptive T cell transfer
        • 1) Homeostatic proliferation(HP)
        • 2) Homeostatic proliferation(HP)下の移入T細胞
        • 3) Homeostatic proliferation(HP)下の細胞移入とTAA vaccination
        • 4) Homeostatic proliferation(HP)下の移入細胞中のCD4+CD25-T細胞とCD4+Treg細胞
          • a. CD4+CD25-T細胞(CD4+T細胞help)
          • b. CD4+Treg細胞
        • 5) Homeostatic proliferation(HP)下の臨床試験
        • 6) Homeostatic proliferation(HP)の抗腫瘍性増強の機作
      • 3. 遺伝子導入T細胞の移入
    • IV. γδT細胞
      • 1. γδT細胞による免疫療法
    • V. Natural killer T cell(NKT細胞)
      • 1. NKT細胞の種類
      • 2. NKT細胞と腫瘍
      • 3. NKT-1細胞の抗腫瘍性機作
      • 4. NKT細胞による免疫療法
    • VI. Th17細胞
      • 1. IL-17/Th17細胞
      • 2. Naive T細胞のTh1細胞, Th2細胞, Th17細胞Treg細胞への分化
      • 3. Th1細胞, Th2細胞, h17細胞, Treg細胞の相互移行
      • 4. IL-17/Th17細胞と腫瘍
  • E. Immunogenic chemotherapy
    P.116閲覧
    • I. Immunogenic anticancer drugの腫瘍への直接作用
    • II. Immunogenic anticancer drugの間接作用(免疫系への作用)
    • III. Immunogenic chemo-immunotherapy
      • 1. Cyclophosphamide(CPA)
        • 1) 前臨床試験
        • 2) 臨床試験
      • 2. Taxan
        • 1) 前臨床試験
        • 2) 臨床試験
      • 3. Gemcitabine(GEM)
        • 1) 前臨床試験
      • 4. Cisplatin(CDDP)
        • 1) 前臨床試験
      • 5. 多剤併用化学療法
    • IV. おわりに
  • F. 腫瘍免疫関連事項
    P.127閲覧
    • I. 腫瘍免疫療法におけるCD4+T細胞の重要性
      • 1. 細胞性免疫成立とCD4+T細胞
        • 1) CD4+T細胞と第I相
          • a. CD4+T/APC/CD8+T細胞の相互作用
          • b. CD4+T/APC相互作用
          • c. APCとしてのCD4+T細胞
          • d. Cross-dressing
        • 2) CD4+T細胞と第II相
        • 3) CD4+T細胞と第III相
      • 2. CD4+T細胞helpとhelp成分
        • 1) CD40/CD40Lシグナル
        • 2) OX40/OX40Lシグナル
        • 3) CD27/CD27Lシグナル
        • 4) 4-1BB/4-1BBLシグナル
        • 5) 第3シグナルとしてのサイトカイン
          • a. IL-2
          • b. IL-12
          • c. IFN-α
          • d. IL-12+IFN-α
          • e. その他のサイトカイン
            • a) IL-15
            • b) IL-7
            • c) IL-21
      • 3. Effector, memory CD8+T細胞の誘導とcognate CD4+T細胞
      • 4. Helepless CD8+T細胞の特性と再生(rescue)
    • I-付. Trogocytosis
      • 1. T細胞, B細胞, 抗原提示細胞(APC)とtrogocytosis
      • 2. NK細胞とtrogocytosis
      • 3. γδT細胞とtrogocytosis
      • 4. CD4-CD8-double negative regulatory T細胞とtrogocytosis
      • 5. Trogocytosisの生物学的意義
        • 1) Th-APC
        • 2) Immune effector clearance
        • 3) Tc-APC
      • 6. HLA-G分子とtrogocytosis
    • II. 腫瘍免疫療法におけるToll-like receptor(TLR)agonistの重要性
      • 1. TLRとそのシグナル伝達
      • 2. TLRシグナルと細胞性免疫
        • 1) TLRシグナルとT細胞
        • 2) TLRシグナルとDC
      • 3. TLRシグナルと腫瘍ワクチン療法
        • 1) TLRシグナルと腫瘍細胞
        • 2) TLR agonist併用の腫瘍ワクチン療法
      • 4. TLRシグナルと既存のanergic, tolerant CTLの回復
        • 1) TLR agonistの全身投与
        • 2) TLR agonistの腫瘍内投与
        • 3) TLR agonistとCD4+T細胞helpの併用
          • a. CD4+T細胞helpの代替としてのTLR agonist
          • b. TLR agonistとCD4+T細胞help成分の併用
  • G. 免疫抑制T細胞
    P.172閲覧
    • I. 免疫抑制T細胞の歴史
    • II. CD4+CD25+regulatory T細胞(Treg細胞)
      • 1. Treg細胞の特性
        • 1) Anergyの測定
        • 2) Suppressionの測定
          • a. 増殖抑制
            • a) 抗CD3抗体刺激抑制試験
            • b) Allo抗原刺激抑制試験
          • b. 機能抑制
        • 3) Cell-contact依存性の測定
        • 4) 液性因子依存性の測定
      • 2. 種類
        • 1) Naturally occurring regulatory T細胞(nTreg細胞)
          • a. nTreg細胞の発生
          • b. Ex vivoでのnTreg細胞の増殖
          • c. Phenotype
            • a) Foxp3
              • i) Foxp3と免疫抑制の分子機構
              • ii) Foxp3の発現様式
              • iii) マウスとヒトでのFoxp3の差異
              • iv) Foxp3とその他の表面マーカーとの関連
            • b) Glucocorticoid-induced TNF-receptor(GITR)
            • c) Cytotoxic T-lymphocyte antigen-4(CTLA-4, CD152)
            • d) Lymphocyte activation gene-3(LAG-3, CD223)
            • e) Gene related to anergy in lymphocyte(GRAIL)
            • f) OX40(CD134)
            • g) CD25(IL-2Rα)
            • h) 4-1BB (CD137)
            • i) Tumor necrosis factor receptor type 2(TNFR2, CD120b)
            • j) CD103(integrin αE chain)
            • k) Neuropilin-1
        • 2) Induced CD4+CD25+regulatory T細胞(iTreg細胞)のin vitroでの誘導
          • a. Foxp3遺伝子の挿入によるiTreg細胞の誘導
          • b. nTreg細胞によるiTreg細胞の誘導
          • c. TGF-βによるiTreg細胞の誘導
          • d. IL-4, IL-13によるiTreg細胞の誘導
          • e. NOによるiTreg細胞の誘導
          • f. α-melanocyte-stimulating hormone(α-MSH)によるiTreg細胞の誘導
          • g. FK778によるiTreg細胞の誘導
          • h. Anti-thymocyte globulin(ATG)によるiTreg細胞の誘導
      • 3. Treg細胞の免疫抑制機作
        • 1) Treg細胞とAPCのクロストークによる抑制
        • 2) その他の抑制機作
          • a. IL-2の欠乏
          • b. Treg細胞産生IFN-γによる抑制
          • c. 免疫抑制性サイトカイン
            • a) IL-10
            • b) TGF-β
            • c) IL-35
            • d) Th1 cytokine mRNA誘導の阻止
          • d. 殺細胞による抑制
            • a) Perforin, granzyme
            • b) Fas/FasL媒介性apoptosis
            • c) Galectin-1
          • e. 代謝障害による抑制
            • a) Adenosine
            • b) COX-2/PGE2
    • III. CD8+regulatory T細胞(CD8+Treg細胞)
      • 1. MHCクラスIa分子拘束性CD8+Treg細胞
        • 1) Cell-contact依存性CD8+Treg細胞
          • a. Naturally occurring CD8+Treg細胞
            • a) CD8+CD25+Treg細胞
              • i) ヒトのCD8+CD25+Treg細胞
              • ii) マウスのCD8+CD25+Treg細胞
            • b) CD8+CD45RClow Treg細胞
            • c) CD8+CD28-Treg細胞
        • 2) サイトカイン産生性CD8+Treg細胞
          • a. Naturally occurring CD8+Treg細胞
            • a) ヒトのTGFβ+IL-10+CD8+CD28-Treg細胞
            • b) マウスのIL-10+CD8+CD122+Treg細胞
            • c) 肝臓内1L-10+CD8+Treg細胞
          • b. Adaptive CD8+Treg細胞
            • a) 抗原非特異的CD8+Treg細胞
              • i) CD8+CD28-Treg細胞
              • ii) CD8+CD103+Treg細胞
            • b) 抗原特異的CD8+Treg細胞
              • i) IL-10+CD8+CD28-Treg細胞
              • ii) TGF-β+CD8+CD25-Treg細胞
      • 2. MHCクラスIb分子拘束性CD8+Treg細胞
        • 1) Qa-1分子拘束性CD8+Treg細胞
          • a. Qa-1分子拘束性CD8+Treg細胞の発生機転
        • 2) CD1d分子拘束性CD8+Treg細胞
      • 3. CD8+CD28-Foxp3+Treg細胞とDCのクロストーク
      • 4. CD4+CD8+ double positive T(DPT)細胞
        • 1) ヒトDP CD25+Foxp3+cytotoxic regulatory T(HOZOT)細胞
        • 2) マウスDPCD25+Foxp3+Treg細胞
      • 5. CD4-CD8- double negative regulatory T(DN Treg)細胞
    • IV. DCによるTreg細胞の誘導
      • 1. DCの種類と成熟
      • 2. 寛容性DCの般的特性
        • 1) IL-10
        • 2) TGF-β
        • 3) Immunoglobulin-like transcript(ILT)-3, ILT-4
        • 4) Indoleamine 2,3-dioxygenase(IDO)
        • 5) B7 family
        • 6) B and T lymphocyte attenuator(BTLA)
      • 3. 生理学的寛容性DCによるTreg細胞の誘導
        • 1) Immature DC(未成熟DC)
        • 2) Semi-mature DC
        • 3) Plasmacytoid DC(pDC)
        • 4) Mucosal tolerance
          • a. Oral tolerance
            • a) 腸管上皮細胞(intestinal epithelial cell, IEC)
            • b) Mucosal associated lymphoid tissue(MALT)関連の寛容性DC
          • b. Skin-induced tolerance
          • c. Nasal tolerance
      • 4. 非生理学的寛容性DCによるTreg細胞の誘導
        • 1) サイトカインによる寛容性DCの誘導
          • a. 1L-10
          • b. TGF-β
          • c. GM-CSF
          • d. M-CSF
          • e. G-CSF
          • f. IL-21, IL-16
          • g. IFN-λ
          • h. Vasoactive intestinal peptide (VIP)
          • i. Hepatocyte growth factor(HGF)
        • 2) 薬剤による寛容性DCの誘導
          • a. Glucocorticoid (GC)
          • b. NF-κB阻害剤今
          • c. TNFシグナル阻害剤
          • d. COX-2阻害剤
          • e. アルコール
          • f. Vitamin D3
          • g. 免疫抑制剤(rapamycin, FK-506, cyclosporin A)
          • h. Retinoic acid
          • i. Antioxidant(vitamin C, vitamin E)
          • j. Estrogen
          • k. 煙草
        • 3) Virus感染による寛容性DCの誘導
      • 5. 寛容性非DC(stromal cell)によるTreg細胞の誘導
        • 1) Mesenchymal stem cell(MSC)
        • 2) Fibroblast
        • 3) Endothelial cell(EC)
  • b. Adaptive CD8+Treg細胞
    P.195閲覧
    • a) CD8+Treg細胞の誘導と抗原
      • i) 抗原の質, 量
      • ii) 抗原の投与回数
    • b) CD8+CD25+Foxp3+Treg細胞
    • c) CD8+CD28-Foxp3+Treg細胞
      • i) In vitroでのCD8+CD28-Treg細胞の誘導
      • ii) 自己免疫疾患のCD8+CD28-Treg細胞
      • iii) 臓器移植時のCD8+CD28-Treg細胞
    • d) IL-10+CD8+CD25-Foxp3-Treg細胞
  • H. まとめ
    P.234閲覧
  • 和文索引
    P.236閲覧
  • 欧文索引
    P.238閲覧
  • 著者略歴
  • 奥付

参考文献

A. 総論 Cancer immunoediting

P.5 掲載の参考文献

P.8 掲載の参考文献

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P.15 掲載の参考文献

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P.22 掲載の参考文献

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C. 手術と免疫

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D. 免疫療法

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E. Immunogenic chemotherapy

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F. 腫瘍免疫関連事項

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G. 免疫抑制T細胞

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