MassIVEapplication/xmlftp://massive-ftp.ucsd.edu/v01/MSV000079125/primaryOK2000000ProteomicsWilliam H. HildebrandTripleTOF 5600Homo Sapiens (ncbitaxon:9606)https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=609107677df9483f8e17973d8be9e282MassIVE24MS:1002864 - No post-translational-modifications are included in the identified peptides of this datasetT 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-β 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.Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells.Carreno Beatriz M BM, Magrini Vincent V, Becker-Hapak Michelle M, Kaabinejadian Saghar S, Hundal Jasreet J, Petti Allegra A AA, Ly Amy A, Lie Wen-Rong WR, Hildebrand William H WH, Mardis Elaine R ER, Linette Gerald P GPInterstitial Dendritic Cells, Dendritic Cells, Veiled Cells, breadth, interdigitating cell, Plasmacytoid Dendritic Cell, Plasmacytoid Dendritic, Veiled Cell, Interdigitating, malignant, Interdigitating Dendritic, Dendritic, Naevocarcinoma, Veiled, Interdigitating Cells, Plasmacytoid, Malignant Melanomas, Interstitial, Malignant, Cell, Plasmacytoid Dendritic Cells, melanoma (disease), Melanomas, Interstitial Dendritic, Melanoma, melanoma, Vaccine, Malignant Melanoma, Cells, veiled cell, Interdigitating Dendritic Cells, Interdigitating Dendritic Cell, Interdigitating Cell, malignant melanoma, Cell., Dendritic Cell, Interstitial Dendritic Cell, reticular cellSvc, melanoma (disease), Bru, Melanomas, Col4a-1, Melanoma, Raw, melanoma, malignant, Malignant Melanoma, malignant melanoma, Del(8)44H, Malignant Melanomas, Naevocarcinoma., MalignantDendritic Cells, breadth, HLAA, Thymus-Dependent Lymphocytes, human being, Interdigitating, Neoplasms, Benign Neoplasm, Receptors, Substitution, T-Lymphocyte, Immunizations, Spectrum Analyses, Tumor, Malignant, White Blood Corpuscle, Human, Mutations, Active Immunization, Responder protein Smok-Tcr, melanoma (disease), T Lymphocyte, melanoma, Homo sapiens, HLA-A, veiled cell, Antigen, Mass, Interdigitating Dendritic Cell, Analysis, Immune., Dendritic Cell, immature T cell, Interstitial Dendritic Cell, Blood Corpuscle, Man, Mass Spectroscopy, Mass Spectrum Analysis, Immune Processes, Immune Responses, Man (Taxonomy), Malignancy, Plasmacytoid Dendritic, Analyses, T-Cells, Interdigitating Dendritic, Dendritic, Naevocarcinoma, T Cell Antigen Receptor, Plasmacytoid, T, PMNC, man, T-Cell Receptors, Neoplasias, T Cells, Immune Response, Immune, Interstitial Dendritic, Clients, mature T cell, Malignancies, Immune Process, T Lymphocytes, Thymus Dependent Lymphocytes, Vaccinations, reticular cell, Lymphocyte, Antigen Receptors, Cancer, Tumors, Interstitial Dendritic Cells, Veiled Cells, HLA A, Leukocyte, Malignant Neoplasm, immune cell, T-Cell Antigen Receptor, Process, T-Cell Receptor, T-Cell Antigen, T-lymphocyte receptor complex, malignant, Modern, Malignant Melanomas, PMN cell, Interstitial, Amino Acid Substitutions, Client, Spectrum Analysis, Cell, results, Antigens, Spectroscopy, Immunization, T Cell Antigen, active immunization, Plasmacytoid Dendritic Cells, Melanomas, 2.7.11.1, MS, Antigen Receptor, Benign, Melanoma, TCR complex, T Cell Receptor, T-Cell, Malignant Melanoma, Neoplasm, Corpuscles, Active, T lymphocyte, Mass Spectrum Analyses, T lymphocyte receptor complex, Blood Cells, Amino Acid, Mass Spectrum, TCR, Tcr, Blood Cell, T-cell, interdigitating cell, Plasmacytoid Dendritic Cell, leucocyte, HLA A Antigens, Veiled Cell, Thymus-Dependent, Veiled, Interdigitating Cells, Spectrometry, Benign Neoplasms, Lymphocytes, patient, Cancers, Substitutions, T-lymphocyte, Active Immunizations, White Blood Corpuscles, human, Thymus-Dependent Lymphocyte, SmokTcr, Malignant Neoplasms, White Blood Cells, white blood cell, Corpuscle, T cell, Patient, Vaccine, Modern Man, T Cell Receptors, Cells, White Blood, Response, T-Cell Antigen Receptors, Interdigitating Dendritic Cells, Dominant negative form of Smok, malignant melanoma, Interdigitating Cell, White, T Cell, T-cell receptor complex, Blood Corpuscles, Receptor, other neoplasm, White Blood Cell, Neoplasia, polymorphonuclear cell0trueSubmission of raw spectrum files for melanoma neoantigensWed Apr 29 13:40:00 BST 2015MSV00007912525837513