Sensitive and frequent identification of high avidity neo-epitope specific CD8+ T cells in immunotherapy-naive ovarian cancer

被引：125

作者：

Bobisse, Sara ^{[1
]}

Genolet, Raphael ^{[1
]}

Roberti, Annalisa ^{[2
]}

Tanyi, Janos L. ^{[2
]}

Racle, Julien ^{[1
,3
]}

Stevenson, Brian J. ^{[3
]}

Iseli, Christian ^{[3
]}

Michel, Alexandra ^{[1
]}

Le Bitoux, Marie-Aude ^{[1
]}

Guillaume, Philippe ^{[1
]}

Schmidt, Julien ^{[1
]}

Bianchi, Valentina ^{[1
]}

Dangaj, Denarda ^{[1
]}

Fenwick, Craig ^{[4
]}

Derre, Laurent ^{[5
]}

Xenarios, Ioannis ^{[3
]}

Michielin, Olivier ^{[1
,3
]}

Romero, Pedro ^{[1
]}

Monos, Dimitri S. ^{[3
,6
]}

Zoete, Vincent ^{[1
,3
]}

Gfeller, David ^{[1
]}

Kandalaft, Lana E. ^{[1
,2
]}

Coukos, George ^{[1
]}

Harari, Alexandre ^{[1
]}

机构：

[1] Univ Lausanne, Ludwig Inst Canc Res, Lausanne Univ Hosp, Dept Oncol, CH-1066 Lausanne, Switzerland

[2] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA

[3] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland

[4] Lausanne Univ Hosp, Dept Med, Div Immunol & Allergy, CH-1066 Lausanne, Switzerland

[5] Lausanne Univ Hosp, Urol Res Unit, CH-1011 Lausanne, Switzerland

[6] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Immunogenet Lab, Philadelphia, PA 19104 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

TUMOR-INFILTRATING LYMPHOCYTES; MULTIPLE SEQUENCE ALIGNMENT; CHIMERIC ANTIGEN RECEPTOR; METASTATIC MELANOMA; CTLA-4; BLOCKADE; PATIENT; NEOANTIGENS; ASSOCIATION; EXPRESSION; REACTIVITY;

D O I：

10.1038/s41467-018-03301-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Immunotherapy directed against private tumor neo-antigens derived from non-synonymous somatic mutations is a promising strategy of personalized cancer immunotherapy. However, feasibility in low mutational load tumor types remains unknown. Comprehensive and deep analysis of circulating and tumor-infiltrating lymphocytes (TILs) for neo-epitope specific CD8(+) T cells has allowed prompt identification of oligoclonal and polyfunctional such cells from most immunotherapy-naive patients with advanced epithelial ovarian cancer studied. Neo-epitope recognition is discordant between circulating T cells and TILs, and is more likely to be found among TILs, which display higher functional avidity and unique TCRs with higher predicted affinity than their blood counterparts. Our results imply that identification of neoepitope specific CD8(+) T cells is achievable even in tumors with relatively low number of somatic mutations, and neo-epitope validation in TILs extends opportunities for mutanomebased personalized immunotherapies to such tumors.

引用

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