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チェックポイントブロックを用いたがん免疫療法

Antoni Ribas1, Jedd D Wolchok2,3

  • 1Department of Medicine, Division of Hematology-Oncology; Department of Surgery, Division of Surgical Oncology; and Department of Molecular and Medical Pharmacology, Jonsson Comprehensive Cancer Center and Parker Institute for Cancer Immunotherapy, University of California, Los Angeles, Los Angeles, CA 90095, USA. aribas@mednet.ucla.edu wolchokj@mskcc.org.

Science (New York, N.Y.)
|March 24, 2018
PubMed
まとめ
この要約は機械生成です。

CTLA-4やPD-1のような免疫チェックポイント阻害剤は 持続的ながん反応をもたらします しかし,抗原表現とインターフェロン-γ経路の変化によって潜在的に獲得された耐性が生じ,新しい組み合わせ戦略が必要になります.

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科学分野:

  • 免疫学と腫瘍学
  • ガン 免疫療法

背景:

  • 細胞毒性Tリンパ球関連タンパク質4 (CTLA-4) とプログラム細胞死1 (PD-1) を標的とした免疫チェックポイント阻害剤は,がん治療に革命をもたらしました.
  • これらの治療は,既存の抗腫瘍T細胞を解放し,様々ながんの多くの患者に持続的な反応をもたらします.

研究 の 目的:

  • がん治療における免疫チェックポイントブロックの有効性を検討する.
  • これらの治療に耐性を持つメカニズムを探求する.
  • 抵抗を克服するための新しい組み合わせ戦略について議論する.

主な方法:

  • 免疫チェックポイント阻害剤に関する既存の臨床データと臨床前研究のレビュー
  • 既得抵抗性の基礎となるメカニズムを分析する.
  • 新興の組み合わせ療法のアプローチの評価

主要な成果:

  • 免疫チェックポイントの封鎖は 重要な患者集団において前例のない 長期的な腫瘍反応を達成します
  • 患者の約3分の1が最終的に再発し,獲得抵抗性の発達を示しています.
  • 新しい証拠によると,耐性メカニズムは抗原表現とインターフェロンγシグナル伝達の変化を含んでいる.

結論:

  • 免疫チェックポイント阻害剤は 効果的ですが 獲得した抵抗性によって 課題に直面します
  • 耐性経路の理解は 患者の治療結果を改善するために不可欠です
  • 次世代の組み合わせ治療は これらの抵抗メカニズムを克服し 抗腫瘍免疫力を高めることに 期待されています