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Identification of two HLA-A*0201 immunogenic epitopes of lactate dehydrogenase C (LDHC): potential novel targets for cancer immunotherapy.
- Source :
- Cancer Immunology, Immunotherapy; Mar2020, Vol. 69 Issue 3, p449-463, 15p
- Publication Year :
- 2020
-
Abstract
- Lactate dehydrogenase C (LDHC) is an archetypical cancer testis antigen with limited expression in adult tissues and re-expression in tumors. This restricted expression pattern together with the important role of LDHC in cancer metabolism renders LDHC a potential target for immunotherapy. This study is the first to investigate the immunogenicity of LDHC using T cells from healthy individuals. LDHC-specific T cell responses were induced by in vitro stimulation with synthetic peptides, or by priming with autologous peptide-pulsed dendritic cells. We evaluated T cell activation by IFN-γ ELISpot and determined cytolytic activity of HLA-A*0201-restricted T cells in breast cancer cell co-cultures. In vitro T cell stimulation induced IFN-γ secretion in response to numerous LDHC-derived peptides. Analysis of HLA-A*0201 responses revealed a significant T cell activation after stimulation with peptide pools 2 (PP2) and 8 (PP8). The PP2- and PP8-specific T cells displayed cytolytic activity against breast cancer cells with endogenous LDHC expression within a HLA-A*0201 context. We identified peptides LDHC<superscript>41−55</superscript> and LDHC<superscript>288−303</superscript> from PP2 and PP8 to elicit a functional cellular immune response. More specifically, we found an increase in IFN-γ secretion by CD8 + T cells and cancer-cell-killing of HLA-A*0201/LDHC positive breast cancer cells by LDHC<superscript>41−55</superscript>- and LDHC<superscript>288−303</superscript>-induced T cells, albeit with a possible antigen recognition threshold. The majority of induced T cells displayed an effector memory phenotype. To conclude, our findings support the rationale to assess LDHC as a targetable cancer testis antigen for immunotherapy, and in particular the HLA-A*0201 restricted LDHC<superscript>41–55</superscript> and LDHC<superscript>288–303</superscript> peptides within LDHC. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03407004
- Volume :
- 69
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Cancer Immunology, Immunotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 143768570
- Full Text :
- https://doi.org/10.1007/s00262-020-02480-4