ArticleJournal for immunotherapy of cancer2021
Protein citrullination as a source of cancer neoantigens.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 43 citations in OpenAlex.
- Tumor-infiltrating plasma cell profiling after PD-1 blockade reveals tumor-specific antibodies.Cancer cell · 2026Article
- Autoantibodies and T Cells Target Citrullinated and Homocitrullinated Antigens in Rheumatoid Arthritis.Immunological reviews · 2026Review
- Immunogenic cell death as a cornerstone for combination therapies with immune checkpoint blockade.Molecular cancer · 2026Review
- Identification of ovarian cancer-associated antigens forming complexes with autoantibodies.Journal of ovarian research · 2026Article
- Profiling Protein Citrullination in Extracellular Vesicles by Single-Molecule Detection Using Direct Stochastic Optical Reconstruction Microscopy.Journal of biophotonics · 2026Article
- Clinical significance of citrullinated glial fibrillary acidic protein in predicting outcomes in hepatocellular carcinoma.World journal of gastrointestinal oncology · 2025Article
- Citrullination in Tumor Metastasis, Inside and Outside the Cells.Cancer science · 2025Review
- Review
- Neoantigen-Driven Immunotherapy in Triple-Negative Breast Cancer: Emerging Strategies and Clinical Potential.Biomedicines · 2025Review
- Surfaceome: a new era in the discovery of immune evasion mechanisms of circulating tumor cells.Molecular oncology · 2025Review
- Citrullination in health and disease: From physiological function to gene regulation.Genes & diseases · 2025Review
- Evaluation of gut leakage and bacterial translocation as efficacy biomarkers of immunotherapy in advanced non-small cell lung cancer (NSCLC).Translational lung cancer research · 2025Article
- Citrullinated ENO1 Vaccine Enhances PD-1 Blockade in Mice Implanted with Murine Triple-Negative Breast Cancer Cells.Vaccines · 2025Article
- Post-Translational Modifications of Proteins Orchestrate All Hallmarks of Cancer.Life (Basel, Switzerland) · 2025Review
- Circulating microRNA Panel for Prediction of Recurrence and Survival in Early-Stage Lung Adenocarcinoma.International journal of molecular sciences · 2024Article
- Breaking tolerance: autoantibodies can target protein posttranslational modifications.Current opinion in biotechnology · 2024Review
- Exploring the Role of Unconventional Post-Translational Modifications in Cancer Diagnostics and Therapy.Current protein & peptide science · 2024Review
- Phosphopeptide Neoantigens as Emerging Targets in Cancer Immunotherapy.Journal of cancer immunology · 2024Article
- Protein citrullination: inhibition, identification and insertion.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Inhibiting MEK1 R189 citrullination enhances the chemosensitivity of docetaxel to multiple tumour cells.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundCitrulline post-translational modification of proteins is mediated by protein arginine deiminase (PADI) family members and has been associated with autoimmune diseases. The role of PADI-citrullinome in immune response in cancer has not been evaluated. We hypothesized that PADI-mediated citrullinome is a source of neoantigens in cancer that induces immune response.
methodsProtein expression of PADI family members was evaluated in 196 cancer cell lines by means of indepth proteomic profiling. Gene expression was assessed using messenger RNA data sets from The Cancer Genome Atlas. Immunohistochemical analysis of PADI2 and peptidyl-citrulline was performed using breast cancer tissue sections. Citrullinated 12-34-mer peptides in the putative Major Histocompatibility Complex-II (MHC-II) binding range were profiled in breast cancer cell lines to investigate the relationship between protein citrullination and antigen presentation. We further evaluated immunoglobulin-bound citrullinome by mass spectrometry using 156 patients with breast cancer and 113 cancer-free controls.
resultsProteomic and gene expression analyses revealed PADI2 to be highly expressed in several cancer types including breast cancer. Immunohistochemical analysis of 422 breast tumor tissues revealed increased expression of PADI2 in ER- tumors (p<0.0001); PADI2 protein expression was positively correlated (p<0.0001) with peptidyl-citrulline staining. PADI2 expression exhibited strong positive correlations with a B cell immune signature and with MHC-II-bound citrullinated peptides. Increased circulating citrullinated antigen-antibody complexes occurred among newly diagnosed breast cancer cases relative to controls (p=0.0012).
conclusionsAn immune response associated with citrullinome is a rich source of neoantigens in breast cancer with a potential for diagnostic and therapeutic applications.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.