Back to Search Start Over

Identification of two HLA-A*0201 immunogenic epitopes of lactate dehydrogenase C (LDHC): potential novel targets for cancer immunotherapy.

Authors :
Thomas R
Shaath H
Naik A
Toor SM
Elkord E
Decock J
Source :
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2020 Mar; Vol. 69 (3), pp. 449-463. Date of Electronic Publication: 2020 Jan 13.
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.

Details

Language :
English
ISSN :
1432-0851
Volume :
69
Issue :
3
Database :
MEDLINE
Journal :
Cancer immunology, immunotherapy : CII
Publication Type :
Academic Journal
Accession number :
31932876
Full Text :
https://doi.org/10.1007/s00262-020-02480-4