Publication Date:
2015-04-04
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549796/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549796/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carreno, Beatriz M -- Magrini, Vincent -- Becker-Hapak, Michelle -- Kaabinejadian, Saghar -- Hundal, Jasreet -- Petti, Allegra A -- Ly, Amy -- Lie, Wen-Rong -- Hildebrand, William H -- Mardis, Elaine R -- Linette, Gerald P -- 5U54HG00307/HG/NHGRI NIH HHS/ -- P30 CA091842/CA/NCI NIH HHS/ -- P30 CA91842/CA/NCI NIH HHS/ -- R21 CA179695/CA/NCI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 May 15;348(6236):803-8. doi: 10.1126/science.aaa3828. Epub 2015 Apr 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA. bcarreno@dom.wustl.edu. ; Genome Institute, Washington University School of Medicine, St. Louis, MO, USA. ; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA. ; Department of Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA. ; EMD Millipore Corporation, Billerica, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25837513" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Substitution/immunology
;
Antigen Presentation
;
Antigens, Neoplasm/genetics/*immunology
;
Cancer Vaccines/immunology/*therapeutic use
;
Dendritic Cells/immunology/*transplantation
;
HLA-A2 Antigen/genetics/*immunology
;
Humans
;
Immunotherapy, Active/*methods
;
Melanoma/genetics/immunology/*therapy
;
Monitoring, Immunologic
;
Mutation
;
Receptors, Antigen, T-Cell, alpha-beta/immunology
;
Skin Neoplasms/genetics/immunology/*therapy
;
T-Lymphocytes/*immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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