The prognostic impact of tumor microenvironment and checkpoint blockade-associated molecules (PD-1, PD-L1, CTLA-4, CD163 AND CD14) in nodal diffuse large B cell lymphoma, NOS

Aim: It is aimed to determine expression of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), CD163 and CD14 which are the molecules related to tumor microenvironment and checkpoint blockade in diffuse large B-cell lymphomas (DLBCL), and also to determine whether these markers, comparing their expressions with prognostic data, may predict prognosis in DBBHL cases. Material and Methods: A total of 52 nodal DLBCL, not otherwise specified (DLBCL, NOS) cases diagnosed between 1998 and 2017 with no known extranodal involvement at the time of diagnosis were evaluated. Clinical prognostic data were obtained in 44 of these cases. PD-1, PD-L1, CD163, CD14 and CTLA-4 were studied by immunohistochemical methods and CTLA-4 marker was excluded from the study due to inability of obtaining proper staining. The relationships between the results and clinical and laboratory prognostic markers were investigated. Results: It was observed that patients with PD-1 expression <5 positive cells/HPF had worse overall survival (p=0.005). No significant relationship was found between survival and PD-L1, CD163 and CD14 expressions. PD-L1 and CD14 staining scores were found to be higher in non-GCB subtype than in GCB subtype. In addition, cases that are >60 years of age, that have ECOG performance score ≥2, stage IV disease, high IPI score (3-5), elevation of LDH, low albumin level, low hemoglobin level, low peripheral blood lymphocyte count, high peripheral blood neutrophil/lymphocyte ratio, high peripheral blood platelet/lymphocyte ratio, MYC ≥40% were found to have worse overall survival. Conclusion: In recent years, the effects of checkpoint and tumor microenvironment related molecules in prognosis of DLBCL, NOS have been extensively investigated. In our study, it was concluded that in patients with low number of PD-1 positive tumor-infiltrating lymphocytes (TILs) have low survival rates and therefore the number of PD-1 positive TILs may be useful in indicating prognosis. On the other hand, there was no significant relationship between survival and PD-L1, CD163 and CD14 expressions. Considering that DLBCL, NOS is a heterogeneous lymphoma group, new studies with large series are needed to obtain more accurate results. Keywords: Diffuse large B-cell lymphoma, tumor microenvironment, PD-1, PD-L1, CD163, CD14