Immunity to X-linked inhibitor of apoptosis protein (XIAP) in malignant melanoma and check-point blockade
Autor: | Anita Giobbie-Hurder, Ryan C. Brennick, F. Stephen Hodi, Jonathan Stevens, Meghna Gupta, Tianqi Chen, Indira Guleria, Jingjing Li, Xinqi Wu, Michael Manos, Jun Zhou |
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Rok vydání: | 2019 |
Předmět: |
CD4-Positive T-Lymphocytes
Enzyme-Linked Immunospot Assay Cancer Research Skin Neoplasms T cell Immunology Epitopes T-Lymphocyte Antineoplastic Agents X-Linked Inhibitor of Apoptosis Protein Ipilimumab Lymphocyte Activation Inhibitor of apoptosis Peripheral blood mononuclear cell Article 03 medical and health sciences 0302 clinical medicine Survivin medicine Humans Immunology and Allergy Melanoma Cells Cultured Cell Proliferation Neoplasm Staging business.industry Cancer medicine.disease Peptide Fragments Immunity Humoral XIAP Treatment Outcome medicine.anatomical_structure Oncology Cancer research Immunotherapy business 030215 immunology medicine.drug |
Zdroj: | Cancer Immunol Immunother |
ISSN: | 1432-0851 0340-7004 |
Popis: | Expression of inhibitors of apoptosis protein (IAP) family members is associated with poor prognosis in cancer patients. Immunity to ML-IAP (livin) and survivin have been well studied in patients with a variety of tumors. XIAP, the most potent inhibitor of apoptosis, is widely expressed in melanoma. To better define its potential role as an immunogenic target, cellular and humoral responses to XIAP were investigated in patients with advanced melanoma. An overlapping peptide library covering the full length of the XIAP protein was used to screen T cell responses of peripheral blood mononuclear cells (PBMC) from stage-IV melanoma patients treated with or without anti-CTLA4 (ipilimumab). The screen identified an array of peptides that predominantly induced CD4(+) T cell responses. XIAP epitope-specific CD4(+) T cells revealed proliferative responses to melanoma cells that express XIAP. Humoral responses to XIAP were also explored. Cellular and humoral responses to XIAP were associated with beneficial clinical outcomes after ipilimumab-based treatment, supporting XIAP as a potential therapeutic target. |
Databáze: | OpenAIRE |
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