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Identification of non-mutated neoantigens presented by TAP-deficient tumors.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2018 Sep 03; Vol. 215 (9), pp. 2325-2337. Date of Electronic Publication: 2018 Aug 16. - Publication Year :
- 2018
-
Abstract
- Most T cell-based immunotherapies of cancer depend on intact antigen presentation by HLA class I molecules (HLA-I). However, defects in the antigen-processing machinery can cause downregulation of HLA-I, rendering tumor cells resistant to CD8 <superscript>+</superscript> T cells. Previously, we demonstrated that a unique category of cancer antigens is selectively presented by tumor cells deficient for the peptide transporter TAP, enabling a specific attack of such tumors without causing immunopathology in mouse models. With a novel combinatorial screening approach, we now identify 16 antigens of this category in humans. These HLA-A*02:01 presented peptides do not derive from the mutanome of cancers, but are of "self" origin and therefore constitute universal neoantigens. Indeed, CD8 <superscript>+</superscript> T cells specific for the leader peptide of the ubiquitously expressed LRPAP1 protein recognized TAP-deficient, HLA-I <superscript>low</superscript> lymphomas, melanomas, and renal and colon carcinomas, but not healthy counterparts. In contrast to personalized mutanome-targeted therapies, these conserved neoantigens and their cognate receptors can be exploited for immune-escaped cancers across diverse histological origins.<br /> (© 2018 Marijt et al.)
- Subjects :
- ATP-Binding Cassette Transporters immunology
CD8-Positive T-Lymphocytes pathology
Female
Humans
Male
Neoplasms pathology
Tumor Cells, Cultured
ATP-Binding Cassette Transporters deficiency
Antigen Presentation
Antigens, Neoplasm immunology
CD8-Positive T-Lymphocytes immunology
HLA-A2 Antigen immunology
LDL-Receptor Related Protein-Associated Protein immunology
Neoplasm Proteins immunology
Neoplasms immunology
Tumor Escape
Subjects
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 215
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 30115740
- Full Text :
- https://doi.org/10.1084/jem.20180577