頭頸部がん患者のHPV特異的なB細胞応答の定義
Andreas Wieland1,2, Mihir R Patel3,4, Maria A Cardenas5
1Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA. andreas.wieland@emory.edu.
Nature
|November 19, 2020
まとめ
ヒトパピローマウイルス (HPV) に特異的なB細胞と抗体分泌細胞は,HPV陽性頭頸部腫瘍に見られる. これらの発見は,腫瘍の微小環境内の局所的な体内免疫反応を明らかにしています.
科学分野:
- 免疫学
- 腫瘍学
- ウイルス学
背景:
- 腫瘍内B細胞とプラズマ細胞は一般的に見られるが,その抗原特異性は不明である.
- 腫瘍の微小環境におけるB細胞の反応を理解することは,がん免疫学にとって極めて重要です.
- ヒトパピローマウイルス (HPV) は頭頸部がんと関連しており,HPV特異的な免疫反応の潜在的な役割を示唆しています.
研究 の 目的:
- HPV陽性頭頸がんにおけるB細胞反応の抗原特異性を調査する.
- 腫瘍マイクロ環境内のHPV特異性B細胞および抗体分泌細胞 (ASC) の存在と機能を特徴付ける.
- 腫瘍に浸透するB細胞の 潜在的治療効果を探るため
主な方法:
- HPV陽性頭頸がん患者の腫瘍サンプルを分析する.
- 様々な免疫検査を用いたHPV特異抗体および抗体分泌細胞 (ASC) の検出
- 腫瘍内B細胞とプラズマ細胞からヒト単体抗体の生成と特徴づけ
- 腫瘍の微小環境内のB細胞集団とその活性化状態を特定するための単細胞RNA配列化.
主要な成果:
- HPVに特異的なB細胞反応は,HPVに特異的なIgG抗体の活発な生成を含む,腫瘍内のin situで検出されました.
- 腫瘍の微小環境でHPV特異のASCが特定され,インフルエンザ特異の細胞の募集は最小限であり,局所反応を示した.
- HPV特異的なASC応答は,E2に対する支配的な応答で,HPVタンパク質E2とE6とE7を標的とした.
- 生成されたHPV特異のモノクローナル抗体は,慢性的な抗原被曝を示唆する高体性高変異を示した.
- 単細胞RNA配列解析により,活性化されたB細胞,生殖中心B細胞,およびASCが発見され,好ましくは腫瘍ストロマに局所され,生殖中心の反応が進行している証拠が示された.
結論:
- 活性化,生殖中心のB細胞およびプラズマ細胞を含む抗原特異のB細胞は,HPV陽性頭頸部がんの腫瘍微環境内に存在し,機能しています.
- これらの発見は,がんにおける体内免疫反応の理解を深める.
- 腫瘍に浸透するB細胞は,新しいがん治療薬の開発の潜在的なターゲットです.
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