Abstract
ContextPD-L1 is an inhibitory ligand that functions as an essential immune checkpoint. FOXP-1 is a member of the FOXP family. STAT-3 plays a critical role in regulation of cell proliferation and survival. The detailed expression of the three markers together in DLBCL tissues and their prognostic value in patients with DLBCL were not fully investigated.Aim was to assess the expression of PD-L1, FOXP-1 and STAT-3 in diffuse large B-cell lymphoma (DLBCL) and to correlate their expression with the pathological findings, prognostic parameters and clinical implications of patients.MethodsPD-L1, FOXP-1 and STAT-3 were assessed in DLBCL tissues derived from 50 patients using immunohistochemistry. Patients were followed up for 3 years for response to therapy progression, recurrence and survival.ResultsHigh PD-L1 expression was associated with bone marrow involvement (p = 0.004), extra-nodal involvement (p = 0.006) and advanced stage (p = 0.003). High FOXP-1 expression was associated with presence of bone marrow involvement and high risk group (p < 0.001). High STAT-3 expression was associated with older age of the patient (p < 0.001), presence of bone marrow involvement (p = 0.002), extra-nodal involvement (p = 0.009), and high risk group (p = 0.005). High expression of PD-L1, FOXP-1 and STAT-3 was related to poor response to therapy, poor OS rate and RFS rates (p < 0.001).ConclusionHigh expression of PD-L1, FOXP-1 and STAT-3 was related poor prognosis in DLBCL patients.
Highlights
Diffuse large B-cell lymphoma (DLBCL) is the commonest histological sub-type of non-Hodgkin lymphomas (NHLs) which occur in adults (Liu et al 2018)
Chemotherapy, radiotherapy and/or combined modalities are described in Table 1 and we correlated the response of therapy to markers expression, we found that high expression of Progressive disease (PD)-L1, Fork-head box protein P-1 (FOXP-1) and Signal transducer and activator of transcription-3 (STAT-3) was related to absent response to chemotherapy, higher incidence of resistance to first line chemotherapy (p = 0.13, 0.030, 0.044 respectively) higher incidence of disease progression poor Overall Survival (OS) rate and Relapse Free Survival (RFS) rates (p < 0.001)
As we have found a positive correlation between Programmed cell death-ligand 1 (PD-L1) expression and FOXP-1 expression and as both markers were associated with poor prognosis in diffuse large B-cell lymphoma (DLBCL) patients, so there is a role of immune dysfunction in such malignancy and both agents may be used as novel prognostic parameters of such cancer as proved by findings of our study
Summary
Diffuse large B-cell lymphoma (DLBCL) is the commonest histological sub-type of non-Hodgkin lymphomas (NHLs) which occur in adults (Liu et al 2018). The development of novel prognostic biomarkers which could be effectively applied to improve the classification and categorization of DLBCL patients according to severity and prognosis is considered an essential need (Liu et al 2018). Programmed cell death-ligand 1 (PD-L1) which is a B7 family member ( known as B7-H1), is an inhibitory ligand that functions as an essential immune checkpoint which plays a role in the regulation of cellular, humoral and adaptive immune responses (LY et al 2017). Several previous studies have reported the expression of PD-L1 in lymphoma and described its relationship with DLBCL prognosis (Kiyasu et al 2015; Westin et al 2014). FOXP-1 plays an important role in many biological processes, ; it is considered a potential oncogene in pancreatic cancer, carcinoma of the liver, and various subtypes of B-cell non-Hodgkin lymphomas (van Keimpema et al 2017). Several studies have evaluated the expression patterns of FOXP1 in DLBCL
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