| Reference | ||
|---|---|---|
| Reference Type | Literature | IEDB_Reference:1030586 |
| Title | HLA ligandomics identifies histone deacetylase 1 as target for ovarian cancer immunotherapy. | |
| Authors | Janet Kerstin Peper; Hans-Christian Bösmüller; Heiko Schuster; Brigitte Gückel; Helen Hörzer; Kevin Roehle; Richard Schäfer; Philipp Wagner; Hans-Georg Rammensee; Stefan Stevanović; Falko Fend; Annette Staebler | |
| Affiliations | Department of Immunology, Institute of Cell Biology, University of Tübingen , Tübingen, Germany; Institute of Pathology, University Hospital of Tübingen , Tübingen, Germany; Department of Obstetrics and Gynecology, University Hospital of Tübingen , Tübingen, Germany; Department of Clinical and Experimental Transfusion Medicine, University Hospital of Tübingen , Tübingen, Germany; Department of Immunology, Institute of Cell Biology, University of Tübingen, Tübingen, Germany; German Cancer Consortium (DKTK), DKFZ partner site Tübingen, Tübingen, Germany; Institute of Pathology, University Hospital of Tübingen, Tübingen, Germany. | |
| Journal | Oncoimmunology | |
| Year | 2016 | |
| Abstract | The recent approval of clincially effective immune checkpoint inhibitors illustrates the potential of cancer immunotherapy. A challenging task remains the identification of specific targets guiding immunotherapy. Facilitated by technical advances, the direct identification of physiologically relevant targets is enabled by analyzing the HLA ligandome of cancer cells. Since recent publications demonstrate the immunogenicity of ovarian cancer (OvCa), immunotherapies, including peptide-based cancer vaccines, represent a promising treatment approach. To identify vaccine peptides, we employed a combined strategy of HLA ligandomics in high-grade serous OvCa samples and immunogenicity analysis. Only few proteins were naturally presented as HLA ligands on all samples analyzed, including histone deacetylase (HDAC) 1 and 2. In vitro priming of CD8(+) T cells demonstrated that two HDAC1/2-derived HLA ligands can induce T-cell responses, capable of killing HLA-matched tumor cells. High HDAC1 expression shown by immunohistochemistry in 136 high-grade serous OvCa patients associated with significantly reduced overall survival (OS), whereas patients with high numbers of CD3(+) tumor-infiltrating lymphocytes (TILs) in the tumor epithelium and CD8(+) TILs in the tumor stroma showed improved OS. However, correlating HDAC1 expression with TILs, high levels of TILs abrogated the impact of HDAC1 on OS. This study strengthens the role of HDAC1/2 as an important tumor antigen in OvCa, demonstrating its impact on OS in a large cohort of OvCa patients. We further identified two immunogenic HDAC1-derived peptides, which frequently induce multi-functional T-cell responses in many donors, suitable for future multi-peptide vaccine trials in OvCa patients. | |
| Curation Last Updated | 2023-08-18 22:43:44 | |
| Epitope | ||
|---|---|---|
| Epitope ID | 54920 | IEDB_epitope:54920 |
| Chemical Type | Linear peptide | |
| Linear Sequence | RMLPHAPGV | |
| Source Molecule Name | histone deacetylase HD1 | |
| Source Organism | Homo sapiens (human) | |
| Starting Position | 371 | |
| Ending Position | 379 | |
| Epitope Reference Details | ||
|---|---|---|
| Epitope Structure Defines | Exact Epitope | |
| Epitope Name | HDAC1 (371-379) | |
| Location of Data in Reference | Table 2 | |
| Immunization | ||
|---|---|---|
| Host Organism | Homo sapiens (human) | |
| Host Details | ||
|---|---|---|
| Sex | F | |
| 1st In Vivo Process | ||
|---|---|---|
| In Vivo Process Type | No immunization | |
| In Vitro Administration | ||
|---|---|---|
| In Vitro Process Type | Primary induction in vitro | |
| Responder Cell Type | PBMC | |
| Stimulator Cell Type | PBMC | |
| In Vitro Immunogen | ||
|---|---|---|
| In Vitro Process Type | Epitope | |
| Chemical Type | Linear peptide | |
| Linear Sequence | RMLPHAPGV | |
| Source Molecule Name | histone deacetylase HD1 | |
| Source Organism | Homo sapiens (human) | |
| Starting Position | 371 | |
| Ending Position | 379 | |
| Immunization Comments | ||
|---|---|---|
| Immunization Comments | The CD8+ T cells were isolated from the blood of healthy donors. Three rounds of in vitro re-stimulation were performed to prime the effector cells. Artificial APCs were generated using streptavidin coated polystyrene beads incubated with 10 nM biotinylated pMHC complexes. | |
| T Cell Assay | ||
|---|---|---|
| Qualitative Measurement | Positive | |
| Method/Technique | intracellular staining | |
| Measurement of | perforin release | |
| Effector Cells | ||
|---|---|---|
| Effector Cell Tissue Type | Blood | |
| Effector Cell Type | T cell CD8+ | |
| Effector Cell Culture Conditions | Short Term Restimulated | |
| Antigen Presenting Cells | ||
|---|---|---|
| Cell Tissue Type | Blood | |
| Cell Type | PBMC | |
| Cell Culture Conditions | Direct Ex Vivo | |
| MHC Allele | ||
|---|---|---|
| MHC Allele Name | HLA-A*02:01 | |
| MHC Evidence Code | MHC binding prediction | |
| Antigen | ||
|---|---|---|
| Epitope Relation | Epitope | |
| Chemical Type | Linear peptide | |
| Linear Sequence | RMLPHAPGV | |
| Source Molecule Name | histone deacetylase HD1 | |
| Source Organism | Homo sapiens (human) | |
| Starting Position | 371 | |
| Ending Position | 379 | |
| Assay Reference Details | ||
|---|---|---|
| Assay Comments by IEDB Curator | CD8+ T cells from healthy blood donors were primed in vitro with the epitope using autologous DCs and B cells. Perforin release was assessed by CD107a production using ICS. | |
| Location of Assay Data in Reference | Figure 2A,C, Fig. S2 | |