メラノーマ細胞によるHLAエクスポートは,免疫回避を促進するために細胞毒性T細胞を誘導する.
- Yoav Chemla 1, Orit Itzhaki 2, Stav Melamed 1, Chen Weller 3, Yuval Sade 1, Paulee Manich 1, Keren Reshef 4, Nicolas Xenidis 1, Avishai Maliah 1, Gilad Levy 5, Roma Parikh 1, Osnat Bartok 3, Opal Levy 1, Itay Tal 1, Gal Aziel 1, Abraham Nissani 6, Sharon Yunger 6, Daniela Likonen 7, Vitaly Kliminsky 7, Tamar Golan 1, Coralie Capron 8, Valentina Ace 1, Ronen Levy 3, Diana Rasoulouniriana 4, Zohar Eyal 9, Yuval Barzilay 9, Roi Balaban 10, Aseel Khateeb 4, Rami Khosravi 11, Amir Grau 12, Tamar Ziv 13, Polina Greenberg 3, Dvir Netanely 14, Hananya Vaknin 15, Xunwei Wu 16, Yael Amitay 17, Ronen Brenner 15, Julia María Martínez Gómez 8, Dov Hershkovitz 18, Tal Yardeni 19, Valentina Zemser-Werner 18, Oren Kobiler 10, Yael Friedmann 20, David Bassan 21, Ron Shamir 14, Lea Eisenbach 21, Nadine Santana-Magal 4, Michael Milyavsky 4, Galit Eisenberg 22, Leeat Keren 17, Merav Cohen 10, Dvir Gur 9, Boaz Barak 23, Michal Lotem 22, David Sprinzak 24, Shoshana Greenberger 10, David Fisher 16, Michal J Besser 25, Mehdi Khaled 26, Pierre Close 27, Ronnie Shapira 6, Sebastien Apcher 26, Asaf Madi 4, Mitchell P Levesque 28, Francessca Rapino 8, Yaron Carmi 4, Shivang Parikh 29, Yardena Samuels 3, Carmit Levy 1
- Yoav Chemla 1, Orit Itzhaki 2, Stav Melamed 1
- 1Department of Human Genetics and Biochemistry, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
- 2Department of Human Genetics and Biochemistry, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 69978, Israel; Ella Lemelbaum Institute for Immuno-Oncology and Melanoma, Sheba Medical Center, Ramat Gan 52621, Israel.
- 3Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
- 4Department of Pathology, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
- 5Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
- 6Ella Lemelbaum Institute for Immuno-Oncology and Melanoma, Sheba Medical Center, Ramat Gan 52621, Israel.
- 7Department of Dermatology, Sheba Medical Center, Ramat Gan, Israel.
- 8Laboratory of Cancer Stemness, GIGA Institute, University of Liège, Liège, Belgium.
- 9Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
- 10Department of Clinical Microbiology and Immunology, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
- 11Single Cell Genomics Core, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
- 12Biomedical Core Facility, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
- 13Smoler Proteomics Center, Lokey Interdisciplinary Center for Life Sciences & Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
- 14Blavatnik School of Computer Science and Artificial Intelligence, Tel Aviv University, Tel Aviv, Israel.
- 15Institute of Oncology, E. Wolfson Medical Center, Holon, Israel.
- 16Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA.
- 17Department of Molecular Cell Biology, Weizmann Institute of Science, Tel Aviv, Israel.
- 18Institute of Pathology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
- 19Metabolic Center, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel.
- 20Bio-Imaging Unit, Hebrew University, Jerusalem 91904, Israel.
- 21Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel.
- 22Hadassah Cancer Research Institute, Hadassah Hebrew University Hospital, Jerusalem, Israel.
- 23Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel; The School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel.
- 24School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.
- 25Ella Lemelbaum Institute for Immuno-Oncology and Melanoma, Sheba Medical Center, Ramat Gan 52621, Israel; Department of Clinical Microbiology and Immunology, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel; Samueli Integrative Pioneering Institute and Davidoff Center, Rabin Medical Center, Petach Tikva, Israel; Felsenstein Cancer Research Center, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
- 26Gustave Roussy Cancer Campus, INSERM U1015, Universite Paris-Saclay, 114 rue Edouard Vaillant, 94800 Villejuif, France.
- 27Laboratory of Cancer Signaling, GIGA Institute, University of Liège, Liège, Belgium.
- 28University of Zurich, Faculty of Medicine, University Hospital of Zurich, Department of Dermatology, Schlieren 8952, Switzerland.
- 29Department of Human Genetics and Biochemistry, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 69978, Israel; Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA.
- 0Department of Human Genetics and Biochemistry, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
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PubMedで要約を見る
まとめ
この要約は機械生成です。メラノーマ細胞は 腫瘍抗原を運ぶメラノソームを放出し T細胞を無効化し 抗腫瘍免疫を阻害します メラノソームの分泌を抑制することで 免疫逃避を減らし 癌治療を助長できます
科学分野
- 免疫学
- 腫瘍学
- 細胞生物学
背景
- メラノマは多くの変異を起こすが T細胞の攻撃に抵抗します
- T細胞は腫瘍の免疫に不可欠ですが メラノーマではしばしば抑制されます
研究 の 目的
- メラノーマがT細胞による免疫を 回避する方法を調べるためだ
- メラノーマの免疫回避の新たなメカニズムを特定する.
- メラノーマの免疫回避を狙った 治療戦略を探るため
主な方法
- 細胞外小胞分析 (メラノソーム)
- 免疫ペプチドミクスとT細胞受容体シーケンシング (TCR-seq)
- メラノーマ患者の生検分析
- メラノソームの分泌を vivo で抑制する.
主要な成果
- メラノーマ細胞によって分泌されるメラノソームには,腫瘍抗原を含むMHC分子が表れます.
- これらのメラノソームはCD8+ T細胞と結合し,機能障害とアポトーシスを引き起こします.
- メラノソームはT細胞の相互作用で腫瘍細胞と競争し,抗腫瘍活動を低下させます.
- メラノームの免疫回避を in vivoで抑制した.
結論
- メラノソームは メラノーマの免疫回避のための 新しいメカニズムを表しています
- メラノソームによるMHCエクスポートは,メラノーマを細胞毒性T細胞から保護する.
- メラノソーム分泌をターゲットにすることで,抗メラノーマ免疫を強化する潜在的治療戦略が提供されます.
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