がん免疫療法の可能性
腫瘍の免疫原性は、がんの種類によってそれぞれ異なります。
固形がんと造血器腫瘍のいずれにおいても、免疫応答が誘導され、初期の増殖が制御されます。これは、がんの免疫原性として知られており、免疫応答の主要な3つの段階「抗原提示」「浸潤」「排除」のいずれにおいても起きていると考えられています1,2。
様々ながんにおけるがん免疫原性のエビデンスの集積は、横断的ながん免疫研究の幅が拡がる根拠となります22。
*代表的ながんを示しますが、すべてを網羅するものではありません。
私たち自身のもつ免疫系の働きにより腫瘍免疫応答が誘導されることは、確固たるエビデンスとして示されています20。さらに、がん免疫の 研究は盛んに行われており、免疫経路を標的とすることによってがん細胞の排除につながることがエビデンスにより示唆されています21。
抗原提示(presentation)
がん細胞はネオアンチゲンを産生するため、免疫系によって非自己として認識されます15,30。
- 悪性黒色腫、非小細胞肺癌(NSCLC)などは遺伝子変異を高度に起こしているがんとされています3。これらの遺伝子変異はネオアンチゲンを産生し、免疫系から認識されやすくなることから、抗腫瘍免疫応答が活性化されることになります4。
浸潤(infiltration)
免疫系の細胞は腫瘍微小環境に浸潤します30。
- 多くの研究から、腫瘍微小環境内には免疫系の細胞が存在することが知られており、さらに、それらの細胞は、がん細胞を認識し遊走してくる能力をもつことが示されています5-18。
排除(elimination)
免疫系の細胞は、外部からの脅威を排除することができます30。
- 何らかの治療介入を行わなくても、腫瘍サイズが縮小する例が報告されています。これは、免疫系ががん細胞を認識し、排除できることを示唆しています19。免疫系を標的とした治療介入を行うことで、免疫系の細胞によるがんの排除が促進されると考えられます。
免疫系ががん細胞を認識し、排除する機構は、I-O研究の基盤となる現象です22。
新たな希望と長期生存の可能性をもつ多くのがん患者さん達の為に、I-O研究は発展を続けます。
免疫系によるがんとの闘いは、生体内の広い範囲でダイナミックに進行します。そのメカニズムを、7つのステップから成る一連のサイクルとして示したのが「がん免疫サイクル(Cancer-Immunity Cycle)」です。
INTRODUCING of Immuno-Oncologyでは、がん免疫サイクルにおける免疫チェックポイント分子の役割とともに、免疫チェックポイント阻害剤の作用機序を解説しています。
【再生時間:6分48秒】
REFERENCES‒がん免疫療法の可能性
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