Contributions
Abstract: PB1754
Type: Publication Only
Background
Programmed cell death-1 (PD-1)/Programmed cell death-ligands (PD-Ls) signal plays a vital role in regulating T-cell response. Several cancers especially EBV-associated malignancy aberrantly express PD-1/PD-Ls leading to immunologic escape of tumors contributing to disease progression. In lymphoma, PD-1/PD-Ls expression was mostly described in Hodgkin lymphoma. Extranodal Natural Killer/T cell lymphoma (ENKTL) is one of the EBV-associated lymphomas more commonly found in Asia. Assessment of PD-1/PD-Ls expression in ENKTL is clinically relevant as a prognostic factor and biomarker for immune checkpoint based therapy.
Aims
To characterize PD-1/PD-Ls expression and its association with clinical characteristics and prognosis of ENKTL.
Methods
Thirty-nine ENKTL patients diagnosed at the King Chulalongkorn Memorial hospital between January 2008 and December 2017. Detailed clinical data was abstracted from medical record and immunohistochemical staining was performed on available formalin fixed paraffin embedded tissue archives to identify PD-1/PD-Ls expression within lymphoma and stromal cells. PD-L1 IHC was stained using the PD-L1 IHC E1L3N rabbit XP monoclonal primary antibody (1:400; Cell Signaling Technology, Danvers, MA, USA). PD-L2 IHC was stained using the rabbit anti-PD-L2 polyclonal antibodies (Sigma-Aldrich, St. Louis, MO, USA; catalogue# SAB3500395-100UG, used at a dilution of 1:1000). IHC staining was evaluated in agreement by two independent pathologists and two hematologists. The 5% cutoff was adopted for the positivity criteria. Clinical, pathological data and outcome were reported.
Results
Of 39 cases, median age at diagnosis was 51 years old. About half of patients presented with advanced stage and high-risk Korean ENKTL Prognostic Index (KPI). Among 33 chemotherapy treated patients, 21 (63.6%) received asparaginase based regimen. PD-L1 and PD-L2 expression were frequently presented within lymphoma cells (n=27; 69.2% for PD-L1 and n=29; 74.4% for PD-L2) with median expression of 15% and 10% respectively. Expression of PD-L1 and PD-L2 were noted on non-tumor stroma of 32 (82.0%) and 0 (0%) patients. Median stromal PD-L1 expression was 5%. PD-1 positivity within stroma was seen in 8 cases (20.5%) with median positive cells of 5% whereas there was no PD-1 expression within lymphoma cells. There was no difference in clinical features between positive and negative PD-1/PD-Ls expression except higher proportion of impaired performance status (PS) among cases with negative PD-L1 within lymphoma cells (P=0.03). There was no correlation between EBV viremia level and PD-1/PD-Ls expression. Positive PD-Ls expression within tumor cells was not associated with different EFS (2-year EFS 45.1 vs 54.7%; P=0.50 for PD-L1 and 42.8 vs 60%; P=0.31 for PD-L2) or OS (2-year OS 48.4 vs 74.1%; P=0.29 for PD-L1 and 51.7 vs 70%; P=0.36 for PD-L2). Neither PD-Ls nor PD-1 expression within stroma was associated with outcome, however, patients with positive stromal PD-1 had trend toward inferior EFS (P=0.08) (Figure 1). Univariable analysis revealed that stage, PS, KPI and asparaginase based treatment as prognostic determining factors.
Conclusion
In ENKTL, PD-Ls were aberrantly expressed within lymphoma cells at high prevalence whereas PD-1/PD-Ls were variably expressed within stroma. Our study did not demonstrate association between PD-1/PD-Ls expression and outcome, however, there was a trend toward worse EFS in patients with positive stromal PD-1. Further studies are warranted to explore significance of PD-1/PD-Ls expression in ENKTL.
Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): lymphoma, NK-T cells, Pathology
Abstract: PB1754
Type: Publication Only
Background
Programmed cell death-1 (PD-1)/Programmed cell death-ligands (PD-Ls) signal plays a vital role in regulating T-cell response. Several cancers especially EBV-associated malignancy aberrantly express PD-1/PD-Ls leading to immunologic escape of tumors contributing to disease progression. In lymphoma, PD-1/PD-Ls expression was mostly described in Hodgkin lymphoma. Extranodal Natural Killer/T cell lymphoma (ENKTL) is one of the EBV-associated lymphomas more commonly found in Asia. Assessment of PD-1/PD-Ls expression in ENKTL is clinically relevant as a prognostic factor and biomarker for immune checkpoint based therapy.
Aims
To characterize PD-1/PD-Ls expression and its association with clinical characteristics and prognosis of ENKTL.
Methods
Thirty-nine ENKTL patients diagnosed at the King Chulalongkorn Memorial hospital between January 2008 and December 2017. Detailed clinical data was abstracted from medical record and immunohistochemical staining was performed on available formalin fixed paraffin embedded tissue archives to identify PD-1/PD-Ls expression within lymphoma and stromal cells. PD-L1 IHC was stained using the PD-L1 IHC E1L3N rabbit XP monoclonal primary antibody (1:400; Cell Signaling Technology, Danvers, MA, USA). PD-L2 IHC was stained using the rabbit anti-PD-L2 polyclonal antibodies (Sigma-Aldrich, St. Louis, MO, USA; catalogue# SAB3500395-100UG, used at a dilution of 1:1000). IHC staining was evaluated in agreement by two independent pathologists and two hematologists. The 5% cutoff was adopted for the positivity criteria. Clinical, pathological data and outcome were reported.
Results
Of 39 cases, median age at diagnosis was 51 years old. About half of patients presented with advanced stage and high-risk Korean ENKTL Prognostic Index (KPI). Among 33 chemotherapy treated patients, 21 (63.6%) received asparaginase based regimen. PD-L1 and PD-L2 expression were frequently presented within lymphoma cells (n=27; 69.2% for PD-L1 and n=29; 74.4% for PD-L2) with median expression of 15% and 10% respectively. Expression of PD-L1 and PD-L2 were noted on non-tumor stroma of 32 (82.0%) and 0 (0%) patients. Median stromal PD-L1 expression was 5%. PD-1 positivity within stroma was seen in 8 cases (20.5%) with median positive cells of 5% whereas there was no PD-1 expression within lymphoma cells. There was no difference in clinical features between positive and negative PD-1/PD-Ls expression except higher proportion of impaired performance status (PS) among cases with negative PD-L1 within lymphoma cells (P=0.03). There was no correlation between EBV viremia level and PD-1/PD-Ls expression. Positive PD-Ls expression within tumor cells was not associated with different EFS (2-year EFS 45.1 vs 54.7%; P=0.50 for PD-L1 and 42.8 vs 60%; P=0.31 for PD-L2) or OS (2-year OS 48.4 vs 74.1%; P=0.29 for PD-L1 and 51.7 vs 70%; P=0.36 for PD-L2). Neither PD-Ls nor PD-1 expression within stroma was associated with outcome, however, patients with positive stromal PD-1 had trend toward inferior EFS (P=0.08) (Figure 1). Univariable analysis revealed that stage, PS, KPI and asparaginase based treatment as prognostic determining factors.
Conclusion
In ENKTL, PD-Ls were aberrantly expressed within lymphoma cells at high prevalence whereas PD-1/PD-Ls were variably expressed within stroma. Our study did not demonstrate association between PD-1/PD-Ls expression and outcome, however, there was a trend toward worse EFS in patients with positive stromal PD-1. Further studies are warranted to explore significance of PD-1/PD-Ls expression in ENKTL.
Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): lymphoma, NK-T cells, Pathology