The inhibitory checkpoint, PD-L2, is a target for effector T cells: Novel possibilities for immune therapy. (1st February 2018)

• Record Type: Journal Article
• 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
• Is Part Of: Oncoimmunology. Volume 7:Number 2(2018)
• Publication Date: 2018-02-01
• Subjects: Anti-cancer immunity -- CD4+ T cells -- CD8+ T cells -- Immune checkpoint regulator -- PD-L2; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2017.1390641
• Languages: English
• ISSNs: 2162-402X

Abstract

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.