Send to

Choose Destination
J Exp Med. 2018 Sep 3;215(9):2325-2337. doi: 10.1084/jem.20180577. Epub 2018 Aug 16.

Identification of non-mutated neoantigens presented by TAP-deficient tumors.

Author information

Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands.
Department of Hematology, Leiden University Medical Center, Leiden, Netherlands.
Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
German Cancer Consortium, German Cancer Research Center, Tübingen, Germany.
Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands


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+ 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+ T cells specific for the leader peptide of the ubiquitously expressed LRPAP1 protein recognized TAP-deficient, HLA-Ilow 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.

[Available on 2019-03-03]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center