Abstract
Objectives
It has been reported that EBV-related lymphomas frequently induce PD-1/PD-L1 upregulation as an adaptive mechanism for tumor immune evasion. Extranodal NK/T-cell lymphomas are strongly associated with EBV infection. We analyzed PD-1/PD-L1 expression in extranodal NK/T-cell lymphoma, nasal type.
Methods
We retrospectively analyzed 11 cases of extranodal NK/T-cell lymphoma, nasal type, diagnosed between 2004 and 2017. Immunohistochemical staining for PD-1 and PD-L1 was performed, and expression was evaluated in tumor cells (TCs) and stromal cells (SCs). Staining of >30% of TCs and >20% of SCs were considered positive. Patient charts were reviewed.
Results
Mean age at diagnosis was 55.6 years (25-81). There were seven males (63.6%) and four females (36.4%). Ten cases (90.9%) were EBV positive (EBER-ISH) and one case (9.1%) was EBV negative. All cases were positive for PD-L1 in SCs, which were tumor-associated macrophages (TAMs) in almost all cases. Two cases (18.2%) also showed PD-L1 overexpression in the TCs. Of these, one case recurred 3 years after diagnosis, with identical PD-1/PD-L1 expression. The other case was lost to follow-up. The remaining nine cases (81.8%) were negative for PD-L1, including the EBV-negative case. All cases were negative for PD-1 in both TCs and SCs. Follow-up information was available for eight patients. Treatments were markedly heterogeneous. None of them received targeted PD-1/PD-L1 blockade. Four patients had no evidence of disease at last follow-up (mean age: 38.3 years). Four patients were deceased or receiving palliative care (mean age: 64.2 years).
Conclusion
In our series of extranodal NK/T-cell lymphoma cases, we observed high frequency of PD-L1 upregulation in TAMs. There was low frequency of PD-L1 upregulation in TCs (18.2%), unlike what has been reported in some studies from Asia (up to 80%). Notably, most of these studies used a cutoff of >5%. All our cases lacked PD-1 expression in both TCs and SCs.
Overexpression of MYC and BCL2 Predicts Poor Prognosis in Patients with Extranodal NK/T-cell Lymphoma, Nasal Type