期刊
CANCER IMMUNOLOGY RESEARCH
卷 5, 期 6, 页码 480-492出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-16-0329
关键词
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资金
- Public Health Service from the National Cancer Institute, NIH [CA180794, CA180820, CA21115, CA66636, CA23318, CA180867, CA39229, CA180844, P50CA101942]
- Department of Health and Human Services
- Claudia Adams Barr Program in Innovative Cancer Research
- AACR Basic Cancer Research Fellowship [14-40-01-MAHO]
- ASCO Young Investigator Award - Kidney Cancer Association
- NIH [CA143832]
- Melanoma Research Alliance
- Sharon Crowley Martin Memorial Fund for Melanoma Research
- Malcolm and Emily MacNaught Fund for Melanoma Research at Dana-Farber Cancer Institute
- Genentech/Roche
- Bristol-Myers Squibb
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. (C)2017 AACR.
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