Autoantibody Landscape in Patients with Advanced Prostate Cancer.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 12 2020
01 12 2020
Historique:
received:
20
05
2020
revised:
03
08
2020
accepted:
16
09
2020
pubmed:
25
9
2020
medline:
15
12
2021
entrez:
24
9
2020
Statut:
ppublish
Résumé
Autoantibody responses in cancer are of great interest, as they may be concordant with T-cell responses to cancer antigens or predictive of response to cancer immunotherapies. Thus, we sought to characterize the antibody landscape of metastatic castration-resistant prostate cancer (mCRPC). Serum antibody epitope repertoire analysis (SERA) was performed on patient serum to identify tumor-specific neoepitopes. Somatic mutation-specific neoepitopes were investigated by associating serum epitope enrichment scores with whole-genome sequencing results from paired solid tumor metastasis biopsies and germline blood samples. A protein-based immunome-wide association study (PIWAS) was performed to identify significantly enriched epitopes, and candidate serum antibodies enriched in select patients were validated by ELISA profiling. A distinct cohort of patients with melanoma was evaluated to validate the top cancer-specific epitopes. SERA was performed on 1,229 serum samples obtained from 72 men with mCRPC and 1,157 healthy control patients. Twenty-nine of 6,636 somatic mutations (0.44%) were associated with an antibody response specific to the mutated peptide. PIWAS analyses identified motifs in 11 proteins, including NY-ESO-1 and HERVK-113, as immunogenic in mCRPC, and ELISA confirmed serum antibody enrichment in candidate patients. Confirmatory PIWAS, Identifying Motifs Using Next-generation sequencing Experiments (IMUNE), and ELISA analyses performed on serum samples from 106 patients with melanoma similarly revealed enriched cancer-specific antibody responses to NY-ESO-1. We present the first large-scale profiling of autoantibodies in advanced prostate cancer, utilizing a new antibody profiling approach to reveal novel cancer-specific antigens and epitopes. Our study recovers antigens of known importance and identifies novel tumor-specific epitopes of translational interest.
Identifiants
pubmed: 32967941
pii: 1078-0432.CCR-20-1966
doi: 10.1158/1078-0432.CCR-20-1966
pmc: PMC7710628
mid: NIHMS1632034
doi:
Substances chimiques
Antigens, Neoplasm
0
Autoantibodies
0
Biomarkers, Tumor
0
Epitopes
0
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6204-6214Subventions
Organisme : NCI NIH HHS
ID : U10 CA180868
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA093373
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA227025
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197633
Pays : United States
Organisme : NIAID NIH HHS
ID : K08 AI139375
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA082103
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA230516
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA186786
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA244118
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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