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The inhibitory checkpoint, PD-L2, is a target for effector T cells: Novel possibilities for immune therapy.

Authors :
Ahmad, Shamaila Munir
Martinenaite, Evelina
Holmström, Morten
Jørgensen, Mia Aaboe
Met, Özcan
Nastasi, Claudia
Klausen, Uffe
Donia, Marco
Pedersen, Lars Møller
Munksgaard, Lars
Ødum, Niels
Woetmann, Anders
Svane, Inge Marie
Andersen, Mads Hald
Source :
OncoImmunology; 2018, Vol. 7 Issue 2, pN.PAG-N.PAG, 1p
Publication Year :
2018

Abstract

Cell surface molecules of the B7/CD28 family play an important role in T-cell activation and tolerance. The relevance of the PD-1/PD-L1 pathway in cancer has been extensively studied whereas PD-L2 has received less attention. However, recently the expression of PD-L2 was described to be independently associated with clinical response in anti-PD1-treated cancer patients. Here, we investigated whether PD-L2 might represent a natural target that induces specific T cells. We identified spontaneous specific T-cell reactivity against two epitopes located in the signal peptide of PD-L2 from samples from patients with cancer as well as healthy individuals ex vivo. We characterized both CD8+and CD4+PD-L2-specific T cells. Interestingly, the epitope in PD-L2 that elicited the strongest response was equivalent to a potent HLA-A2-restricted epitope in PD-L1. Importantly, PD-L1-specific and PD-L2-specific T cells did not cross-react; therefore, they represent different T-cell antigens. Moreover, PD-L2-specific T cells reacted to autologous target cells depending on PD-L2 expression. These results suggested that activating PD-L2 specific T cells (e.g., by vaccination) might be an attractive strategy for anti-cancer immunotherapy. Accordingly, PD-L2 specific T cells can directly support anti-cancer immunity by killing of target cells, as well as, indirectly, by releasing pro-inflammatory cytokines at the microenvironment in response to PD-L2-expressing immune supressive cells. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
21624011
Volume :
7
Issue :
2
Database :
Complementary Index
Journal :
OncoImmunology
Publication Type :
Academic Journal
Accession number :
126995394
Full Text :
https://doi.org/10.1080/2162402X.2017.1390641