TY - JOUR
T1 - Autoantibody landscape in patients with advanced prostate cancer
AU - Chen, William S.
AU - Haynes, Winston A.
AU - Waitz, Rebecca
AU - Kamath, Kathy
AU - Vega-Crespo, Agustin
AU - Shrestha, Raunak
AU - Zhang, Minlu
AU - Foye, Adam
AU - Carretero, Ignacio Baselga
AU - Garcilazo, Ivan Perez
AU - Zhang, Meng
AU - Zhao, Shuang G.
AU - Sjöström, Martin
AU - Quigley, David A.
AU - Chou, Jonathan
AU - Beer, Tomasz M.
AU - Rettig, Matthew
AU - Gleave, Martin
AU - Evans, Christopher P.
AU - Lara, Primo
AU - Chi, Kim N.
AU - Reiter, Robert E.
AU - Alumkal, Joshi J.
AU - Ashworth, Alan
AU - Aggarwal, Rahul
AU - Small, Eric J.
AU - Daugherty, Patrick S.
AU - Ribas, Antoni
AU - Oh, David Y.
AU - Shon, John C.
AU - Feng, Felix Y.
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/12
Y1 - 2020/12
N2 - Purpose: 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). Experimental Design: 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. Results: 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. Conclusions: 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.
AB - Purpose: 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). Experimental Design: 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. Results: 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. Conclusions: 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.
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U2 - 10.1158/1078-0432.CCR-20-1966
DO - 10.1158/1078-0432.CCR-20-1966
M3 - Article
C2 - 32967941
AN - SCOPUS:85101029523
SN - 1078-0432
VL - 26
SP - 6204
EP - 6214
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 23
ER -