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Paucity of PD-L1 expression in prostate cancer: innate and adaptive immune resistance
A M Martin1, T R Nirschl1, C J Nirschl1
1Department of Oncology, Johns Hopkins University, Baltimore, MD, USA.
Background:
Primary prostate cancers are infiltrated with programmed death-1 (PD-1) expressing CD8+ T-cells. However, in early clinical trials, men with metastatic castrate-resistant prostate cancer did not respond to PD-1 blockade as a monotherapy. One explanation for this unresponsiveness could be that prostate tumors generally do not express programmed death ligand-1 (PD-L1), the primary ligand for PD-1. However, lack of PD-L1 expression in prostate cancer would be surprising, given that phosphatase and tensin homolog (PTEN) loss is relatively common in prostate cancer and several studies have shown that PTEN loss correlates with PD-L1 upregulation--constituting a mechanism of innate immune resistance. This study tested whether prostate cancer cells were capable of expressing PD-L1, and whether the rare PD-L1 expression that occurs in human specimens correlates with PTEN loss.
Methods:
Human prostate cancer cell lines were evaluated for PD-L1 expression and loss of PTEN by flow cytometry and western blotting, respectively. Immunohistochemical (IHC) staining for PTEN was correlated with PD-L1 IHC using a series of resected human prostate cancer samples.
Results:
In vitro, many prostate cancer cell lines upregulated PD-L1 expression in response to inflammatory cytokines, consistent with adaptive immune resistance. In these cell lines, no association between PTEN loss and PD-L1 expression was apparent. In primary prostate tumors, PD-L1 expression was rare, and was not associated with PTEN loss.
Conclusions:
These studies show that some prostate cancer cell lines are capable of expressing PD-L1. However, in human prostate cancer, PTEN loss is not associated with PD-L1 expression, arguing against innate immune resistance as a mechanism that mitigates antitumor immune responses in this disease.
Insights
Prostate cancer cells can express programmed death ligand-1 (PD-L1), but PTEN loss does not correlate with PD-L1 expression in human tumors, challenging innate immune resistance theories.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Prostate tumors have CD8+ T-cells but limited response to PD-1 blockade.
- Prostate cancer often lacks PD-L1 expression, hindering PD-1 blockade efficacy.
- PTEN loss, common in prostate cancer, typically upregulates PD-L1, suggesting immune resistance.
Purpose of the Study:
- To investigate if prostate cancer cells can express PD-L1.
- To determine if PD-L1 expression in human prostate cancer correlates with PTEN loss.
Main Methods:
- Prostate cancer cell lines assessed for PD-L1 and PTEN via flow cytometry and western blotting.
- Immunohistochemistry used to correlate PTEN and PD-L1 in human prostate cancer samples.
Main Results:
- Prostate cancer cell lines upregulated PD-L1 with inflammatory cytokines in vitro.
- No association found between PTEN loss and PD-L1 expression in cell lines.
- PD-L1 expression was rare in primary prostate tumors and not linked to PTEN loss.
Conclusions:
- Prostate cancer cells demonstrate capacity for PD-L1 expression.
- PTEN loss is not associated with PD-L1 expression in human prostate cancer.
- Innate immune resistance via PTEN loss-mediated PD-L1 upregulation is unlikely in this disease.
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