Journal
SCIENCE
Volume 348, Issue 6236, Pages 803-808Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaa3828
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Funding
- Barnes-Jewish Hospital Foundation
- Siteman Cancer Frontier Fund
- Our Mark on Melanoma (MOM) Foundation
- Come Out Swinging (COS) Foundation
- Blackout Melanoma Foundation
- National Cancer Institute [P30 CA91842, R21 CA179695]
- National Human Genome Research Institute [5U54HG00307]
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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.
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