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- W2885871434 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+ 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." @default.
- W2885871434 created "2018-08-22" @default.
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- W2885871434 date "2018-08-16" @default.
- W2885871434 modified "2023-10-16" @default.
- W2885871434 title "Identification of non-mutated neoantigens presented by TAP-deficient tumors" @default.
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- W2885871434 doi "https://doi.org/10.1084/jem.20180577" @default.
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