HLA-restricted CTL that are specific for the immune checkpoint ligand PD-L1 occur with high frequency in cancer patients.

Shamaila Munir, Gitte Holmen Andersen, Ozcan Met, Marco Donia, Thomas Mørch Frøsig, Stine Kiaer Larsen, Tobias Wirenfeldt Klausen, Inge Marie Svane, Mads Hald Andersen

Research output: Contribution to journalJournal articleResearchpeer-review


PD-L1 (CD274) contributes to functional exhaustion of T cells and limits immune responses in patients with cancer. In this study, we report the identification of an human leukocyte antigen (HLA)-A2–restricted epitope from PD-L1, and we describe natural, cytolytic T-cell reactivity against PD-L1 in the peripheral blood of patients with cancer and healthy individuals. Notably, PD-L1–specific T cells were able not only to recognize and kill tumor cells but also PD-L1–expressing dendritic cells in a PD-L1–dependent manner, insofar as PD-L1 ablation rescued dendritic cells from killing. Furthermore, by incubating nonprofessional antigen-presenting cells with long peptides from PD-L1, we found that PD-L1 was rapidly internalized, processed, and cross-presented by HLA-A2 on the cell surface. Apparently, this cross-presentation was TAP-independent, as it was conducted not only by B cells but in addition by TAP-deficient T2-cells. This is intriguing, as soluble PD-L1 has been detected in the sera from patients with cancer. PD-L1–specific CTL may boost immunity by the killing of immunosuppressive tumor cells as well as regulatory cells. However, PD-L1–specific CTLs may as well suppress immunity by the elimination of normal immune cells especially PD-L1 expressing mature dendritic cells.
Original languageEnglish
JournalCancer Research
Issue number6
Pages (from-to)1764-1776
Number of pages14
Publication statusPublished - 2013
Externally publishedYes


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