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A comparative view on the expression patterns of PD-L1 and PD-1 in soft tissue sarcomas.
Cancer Immunol. Immunother. 69, 1353-1362 (2020)
Soft tissue sarcomas (STSs) are heterogeneous cancers associated with poor prognosis due to high rates of local recurrence and metastasis. The programmed death receptor ligand 1 (PD-L1) is expressed in several cancers. PD-L1 interacts with its receptor, PD-1, on the surface of tumor-infiltrating lymphocytes (TILs), thereby attenuating anti-cancer immune response. Immune checkpoint inhibitors targeting this interaction have been established as effective anti-cancer drugs. However, studies on the PD-L1 and PD-1 expression status in STS are commonly limited by small sample size, analysis of single STS subtypes, or lack of combinatorial marker assessment. To overcome these limitations, we evaluated the expression patterns of intratumoral PD-L1, the number of TILs, their PD-1 expression, and associations with clinicopathological parameters in a large and comprehensive cohort of 225 samples comprising six STS subtypes. We found that nearly all STS subtypes showed PD-L1 expression on the tumor cells, albeit with a broad range of positivity across subtypes (50% angiosarcomas to 3% synovial sarcomas). Co-expression and correlation analyses uncovered that PD-L1 expression was associated with more PD-1-positive TILs (P < 0.001), higher tumor grading (P = 0.016), and worse patients’ 5-year overall survival (P = 0.028). The results were in line with several publications on single STS subtypes, especially when comparing findings for STS with low and high mutational burden. In sum, the substantial portion of PD-L1 positivity, the co-occurrence of PD-1-positive TILs, and the association of PD-L1 with unfavorable clinical outcome provide rationales for immune checkpoint inhibition in patients with PD-L1-positive STS.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Immune Checkpoint Inhibition ; Pd-1 ; Pd-l1 ; Soft Tissue Sarcoma ; Tumor-infiltrating Lymphocytes; Retrospective Analysis; Nivolumab; Blockade; Ipilimumab; Biomarkers; Efficacy; Receptor; Phase-2; Safety; Cells
ISSN (print) / ISBN
0340-7004
e-ISSN
1432-0851
Journal
Cancer Immunology, Immunotherapy
Quellenangaben
Volume: 69,
Issue: 7,
Pages: 1353-1362
Publisher
Springer
Publishing Place
One New York Plaza, Suite 4600, New York, Ny, United States
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
CF Immunoanalytics (IMA)