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Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a
Toshihiro Nagato1,2, Takayuki Ohkuri3, Kenzo Ohara4,3
1Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, 078-8510, Japan. rijun@asahikawa-med.ac.jp.
Abstract:
Nasal natural killer/T-cell lymphoma (NNKTL) is an aggressive neoplasm with poor therapeutic responses and prognosis. The programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway plays an important role in immune evasion of tumor cells through T-cell exhaustion. The aim of the present study was to examine the expression of PD-L1 and PD-1 molecules in NNKTL. We detected the expression of PD-L1 in biopsy samples from all of the NNKTL patients studied. PD-L1 was found on both malignant cells and tumor-infiltrating macrophages, while PD-1-positive mononuclear cells infiltrated the tumor tissues in 36% of patients. Most significantly, soluble PD-L1 (sPD-L1) was present in sera of NNKTL patients at higher levels as compared to healthy individuals and the levels of serum sPD-L1 in patients positively correlated with the expression of PD-L1 in lymphoma cells of tumor tissues. In addition, the high-sPD-L1 group of patients showed significantly worse prognosis than the low-sPD-L1 group. Furthermore, we confirmed that membrane and soluble PD-L1 was expressed on the surface and in the culture supernatant, respectively, of NNKTL cell lines. The expression of PD-L1 was observed in tumor tissues and sera from a murine xenograft model inoculated with an NNKTL cell line. Our results suggest that sPD-L1 could be a prognostic predictor for NNKTL and open up the possibility of immunotherapy of this lymphoma using PD-1/PD-L1 axis inhibitors.
Insights
Soluble PD-L1 (sPD-L1) is elevated in nasal NK/T-cell lymphoma (NNKTL) patients and correlates with disease progression. This finding suggests sPD-L1 may predict prognosis and support immunotherapy for NNKTL.
Area of Science:
- Oncology
- Immunology
Background:
- Nasal natural killer/T-cell lymphoma (NNKTL) is an aggressive cancer with limited treatment options.
- The programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway is implicated in tumor immune evasion via T-cell exhaustion.
Purpose of the Study:
- To investigate the expression of PD-L1 and PD-1 in NNKTL.
- To evaluate the clinical significance of soluble PD-L1 (sPD-L1) in NNKTL patients.
Main Methods:
- Analysis of PD-L1 and PD-1 expression in NNKTL biopsy samples.
- Quantification of serum sPD-L1 levels in patients and healthy controls.
- Correlation of sPD-L1 levels with clinical data and tumor PD-L1 expression.
- Validation in NNKTL cell lines and a murine xenograft model.
Main Results:
- PD-L1 expression was detected on malignant cells and macrophages in NNKTL tissues.
- PD-1-positive immune cells were found in 36% of tumor samples.
- Serum sPD-L1 levels were significantly higher in NNKTL patients compared to controls.
- Elevated serum sPD-L1 correlated with increased tumor PD-L1 expression and poorer prognosis.
Conclusions:
- Soluble PD-L1 is a potential prognostic biomarker for NNKTL.
- Targeting the PD-1/PD-L1 axis may offer a therapeutic strategy for NNKTL.
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