A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells

被引：1013

作者：

Carreno, Beatriz M. ^{[1
]}

Magrini, Vincent ^{[2
]}

Becker-Hapak, Michelle ^{[1
]}

Kaabinejadian, Saghar ^{[3
]}

Hundal, Jasreet ^{[2
]}

Petti, Allegra A. ^{[2
]}

Ly, Amy ^{[2
]}

Lie, Wen-Rong ^{[4
]}

Hildebrand, William H. ^{[3
]}

Mardis, Elaine R. ^{[2
]}

Linette, Gerald P. ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Genome Inst, St Louis, MO USA

[3] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA

[4] EMD Millipore Corp, Billerica, MA USA

来源：

SCIENCE | 2015年 / 348卷 / 6236期

关键词：

CANCER-IMMUNOTHERAPY; EPITOPE DISCOVERY; VIRUS-INFECTION; TUMOR-ANTIGENS; LYMPHOCYTES; IDENTIFICATION; PATIENT; RECOGNITION; REPERTOIRE; RESISTANCE;

D O I：

10.1126/science.aaa3828

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：

T cell immunity directed against tumor-encoded amino acid substitutions occurs in some melanoma patients. This implicates missense mutations as a source of patient-specific neoantigens. However, a systematic evaluation of these putative neoantigens as targets of antitumor immunity is lacking. Moreover, it remains unknown whether vaccination can augment such responses. We found that a dendritic cell vaccine led to an increase in naturally occurring neoantigen-specific immunity and revealed previously undetected human leukocyte antigen (HLA) class I-restricted neoantigens in patients with advanced melanoma. The presentation of neoantigens by HLA-A* 02: 01 in human melanoma was confirmed by mass spectrometry. Vaccination promoted a diverse neoantigen-specific T cell receptor (TCR) repertoire in terms of both TCR-beta usage and clonal composition. Our results demonstrate that vaccination directed at tumor-encoded amino acid substitutions broadens the antigenic breadth and clonal diversity of antitumor immunity.

引用

页码：803 / 808

页数：6

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