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T cells specific for a TAP-independent self-peptide remain naïve in tumor-bearing mice and are fully exploitable for therapy
- Source :
- OncoImmunology, Vol 7, Iss 3 (2018)
- Publication Year :
- 2018
- Publisher :
- Taylor & Francis Group, 2018.
-
Abstract
- Cancers frequently evade immune-recognition by lowering peptide:MHC-I complexes on their cell surface. Limited peptide supply due to TAP-deficiency results in such MHC-Ilow immune-escape variants. Previously, we reported on a category of TAP-independent self-peptides, called TEIPP, with selective presentation by these tumors. Here we demonstrate that in contrast to T cells specific for conventional tumor antigens, TEIPP-directed T cells remain naïve in mice bearing immune-escaped tumors. This unaffected state was caused by low levels of MHC-I on the tumors and the failure to cross-present low levels of antigenic protein by host APCs. Importantly, increased levels of MHC-I, antigen or co-stimulation resulted in potent activation of TEIPP-specific T cells via direct presentation. Genetic knockdown by CRISPR/Cas9 technology of the relevant MHC-I allele in tumor cells indeed abrogated T cell activation. Vaccine-mediated priming of TEIPP-specific T cells induced efficient homing to MHC-Ilow tumors and subsequently protected mice against outgrowth of their MHC-Ilow tumor. Thus, our data open up the search of TEIPP-specific T cells in cancer patients to explore their application against MHC-Ilow tumor cells.
Details
- Language :
- English
- ISSN :
- 2162402X
- Volume :
- 7
- Issue :
- 3
- Database :
- Directory of Open Access Journals
- Journal :
- OncoImmunology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.2e0ac7b3d434c328ea6ff06848bbc5a
- Document Type :
- article
- Full Text :
- https://doi.org/10.1080/2162402X.2017.1382793