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Cancer Immunol Res. 2017 Jun;5(6):480-492. doi: 10.1158/2326-6066.CIR-16-0329. Epub 2017 May 18.

Soluble PD-L1 as a Biomarker in Malignant Melanoma Treated with Checkpoint Blockade.

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
2
Melanoma Disease Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
3
Center for Immuno-oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
4
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
5
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
6
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
7
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
8
Immunologic Monitoring and Cellular Products Laboratory, Hillman Cancer Center Research Pavilion, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
9
Biomedical Research Laboratories, Medicine Faculty, Catholic University of Maule, Talca, Chile.
10
Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
11
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. stephen_hodi@dfci.harvard.edu.

Abstract

Blockade of the pathway including programmed death-ligand 1 (PD-L1) and its receptor programmed cell death protein 1 (PD-1) has produced clinical benefits in patients with a variety of cancers. Elevated levels of soluble PD-L1 (sPD-L1) have been associated with worse prognosis in renal cell carcinoma and multiple myeloma. However, the regulatory roles and function of sPD-L1 particularly in connection with immune checkpoint blockade treatment are not fully understood. We identified four splice variants of PD-L1 in melanoma cells, and all of them are secreted. Secretion of sPD-L1 resulted from alternate splicing activities, cytokine induction, cell stress, cell injury, and cell death in melanoma cells. Pretreatment levels of sPD-L1 were elevated in stage IV melanoma patient sera compared with healthy donors. High pretreatment levels of sPD-L1 were associated with increased likelihood of progressive disease in patients treated by CTLA-4 or PD-1 blockade. Although changes in circulating sPD-L1 early after treatment could not distinguish responders from those with progressive disease, after five months of treatment by CTLA-4 or PD-1 blockade patients who had increased circulating sPD-L1 had greater likelihood of developing a partial response. Induction of sPD-L1 was associated with increased circulating cytokines after CTLA-4 blockade but not following PD-1 blockade. Circulating sPD-L1 is a prognostic biomarker that may predict outcomes for subgroups of patients receiving checkpoint inhibitors. Cancer Immunol Res; 5(6); 480-92. ©2017 AACR.

PMID:
28522460
PMCID:
PMC5642913
DOI:
10.1158/2326-6066.CIR-16-0329
[Indexed for MEDLINE]
Free PMC Article

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