Abstract
Background: Natural killer/T-cell lymphoma (NKTCL) is a highly aggressive lymphoma with a dismal prognosis, and novel therapeutic targets are urgently needed. Programmed death-ligand 1 (PD-L1) has become a promising therapeutic target for various cancers, but most of the studies have focused on expression of PD-L1 on tumor cells. Expression of PD-L1 on tumor-infiltrating non-malignant cells, especially monocytes, has not been studied in NKTCL, and its prognostic value remains unknown.Materials and Methods: Expression of PD-L1 on tumor-infiltrating stromal cells was measured in NKTert and HS5 cells when cultured alone or co-cultured with NKTCL cell lines. Clinical samples were collected from 42 patients with newly diagnosed NKTCL. Expression of PD-L1 on monocytes was analyzed in patients' peripheral blood and tumor tissues using flow cytometry and immunofluorescent staining, respectively. Survival data were retrospectively collected and the prognostic significance of PD-L1 expression on monocytes was analyzed.Results: PD-L1 expression on tumor-infiltrating stromal cells was remarkably elevated when co-cultured with NKTCL cells. The percentage of PD-L1+ monocytes among all monocytes in peripheral blood was significantly higher in NKTCL patients than that in healthy individuals. Among NKTCL patients, percentage of PD-L1+ monocytes in blood positively correlated with that in tumor tissues. Patients with a higher percentage (≥78.2%) of PD-L1+ monocytes in blood or with a higher percentage (≥24.2%) of PD-L1+ monocytes in tumor tissues exhibited a significantly inferior survival, compared with their counterparts. A higher percentage of PD-L1+ monocytes in blood or tumor tissues was an independent adverse prognostic factor.Conclusions: Expression of PD-L1 on monocytes is up-regulated and has significant prognostic value in patients with NKTCL.
Highlights
Natural killer/T-cell lymphoma (NKTCL) is a distinct subtype of non-Hodgkin lymphoma in World Health Organization (WHO) classification of hematopoietic and lymphoid malignancies [1,2,3]
The percentage of PD-L1+ monocytes among all monocytes in peripheral blood was significantly higher in NKTCL patients than that in healthy individuals
We retrospectively examined the levels of PD-L1 expression on monocytes in peripheral blood and paraffin-embedded tumor tissues in 42 patients with newly diagnosed NKTCL
Summary
Natural killer/T-cell lymphoma (NKTCL) is a distinct subtype of non-Hodgkin lymphoma in World Health Organization (WHO) classification of hematopoietic and lymphoid malignancies [1,2,3]. This disease exhibits highly aggressive histological and clinical features with a dismal prognosis [4, 5]. Natural killer/T-cell lymphoma (NKTCL) is a highly aggressive lymphoma with a dismal prognosis, and novel therapeutic targets are urgently needed. Programmed death-ligand 1 (PD-L1) has become a promising therapeutic target for various cancers, but most of the studies have focused on expression of PD-L1 on tumor cells. Expression of PD-L1 on tumor-infiltrating non-malignant cells, especially monocytes, has not been studied in NKTCL, and its prognostic value remains unknown
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