PMID- 23328583
OWN - NLM
STAT- MEDLINE
DCOM- 20130805
LR  - 20210103
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 73
IP  - 6
DP  - 2013 Mar 15
TI  - HLA-restricted CTL that are specific for the immune checkpoint ligand PD-L1 occur 
      with high frequency in cancer patients.
PG  - 1764-76
LID - 10.1158/0008-5472.CAN-12-3507 [doi]
AB  - 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.
FAU - Munir, Shamaila
AU  - Munir S
AD  - Center for Cancer Immune Therapy, Department of Hematology and Oncology, 
      Copenhagen University Hospital, Herlev, Herlev Ringvej, Herlev, Denmark.
FAU - Andersen, Gitte Holmen
AU  - Andersen GH
FAU - Met, Ozcan
AU  - Met O
FAU - Donia, Marco
AU  - Donia M
FAU - Frosig, Thomas Morch
AU  - Frosig TM
FAU - Larsen, Stine Kiaer
AU  - Larsen SK
FAU - Klausen, Tobias Wirenfeldt
AU  - Klausen TW
FAU - Svane, Inge Marie
AU  - Svane IM
FAU - Andersen, Mads Hald
AU  - Andersen MH
LA  - eng
PT  - Journal Article
DEP - 20130117
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - B7-H1 Antigen/*metabolism
MH  - Case-Control Studies
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - Neoplasms/*immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
EDAT- 2013/01/19 06:00
MHDA- 2013/08/06 06:00
CRDT- 2013/01/19 06:00
PHST- 2013/01/19 06:00 [entrez]
PHST- 2013/01/19 06:00 [pubmed]
PHST- 2013/08/06 06:00 [medline]
AID - 0008-5472.CAN-12-3507 [pii]
AID - 10.1158/0008-5472.CAN-12-3507 [doi]
PST - ppublish
SO  - Cancer Res. 2013 Mar 15;73(6):1764-76. doi: 10.1158/0008-5472.CAN-12-3507. Epub 
      2013 Jan 17.