Evaluation of PD-1 AND PD-L1 expression of de novo and transformed diffuse large b cell lymphomas

Diffuse large B-cell lymphoma (DLBCL) is a mature B cell neoplasm constituting 25-35% of non-Hodgkin lymphomas, with a 5-year overall survival rate of 65%. The development of DLBCL occurs de novo or by transformation of a low grade B cell neoplasia. There are different mechanisms between these two pathways, and the prognosis of most transformed DLBCLs is worse than de novo DLBCL. Programmed death receptor (PD-1) and programmed death ligand (PD-L1) are effective physiological molecules in the regulation of the immune system. These molecules have been shown in many solid tumors and hematolymphoid malignancies and are effective in the escape of tumor cells from the immune system. In recent years, PD-1 and PD-L1 molecules have become important targets in immunotherapy, especially in solid tumors and their microenvironment. In this study, 57 patients of DLBCL transformed from low grade B-cell lymphoma diagnosed between 2000 and 2016, and 58 patients with an initial diagnoses of de novo DLBCL in the period of 2010-2016 were assessed with immunohistochemical method, for the immunoexpression levels of PD-1 and PD-L1 markers in tumor cells and microenvironment. The relationship between morphological and other immunohistochemical parameters, and the correlation of these findings with each other were investigated In the study, the mean age and gender distribution (male: female ratio) were 61.8 years old and 0.7 in transformed group, 59.5 years old and 0.8 in de novo group, respectively, and the two groups had a similar distribution. The involvement of the bone marrow in staging biopsies were 35% in the transformed group and 13.5% in the de novo group. According to the Hans algorithm, 29 (50.9%) cases in the transformed group were GCB, 28 (49.1%) were non-GCB/ABC; in the de novo group, 24 (41.4%) were GCB and 34 (58.6%) were non-GCB/ABC subtypes. Tumor infiltrating lymphocyte and tumor positivity of PD-1 were found in 56 (98.2%) and 20 (35.1%) cases in the transformed group; 49 (84.5%) and 14 (24.1%) cases in the de novo group, respectively. Microenvironment and tumor positivity of PD-L1 were found in 46 (80.7%) and 10 (17.5%) cases in the transformed group; 57 (98.3%) and 11 (19%) patients in the de novo group, respectively. In the transformed group, eight cases (40%) with PD-1 positive tumor cells had a history of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), five (50%) cases with PD-L1 positive tumor cells had a history of marginal zone lymphoma. The number of cases with PD-1 positive tumor infiltrating lymphocytes was higher in de novo group and this result was statistically significant. When PD-1 and PD-L1 expressions were compared, a positive correlation was found between the level of PD-1 positive tumor infiltrating lymphocytes and PD-L1 positivity in the microenvironment of both the transformed and de novo group. There was no significant relationship between PD-1 and PD-L1 expression levels in tumor microenvironment and in tumor cells and overall survival. In our study, there was no difference between PD-1 and PD-L1 expression levels in tumor cells, in this group of cases with two pathogenetically different pathways. In both groups, the correlation of PD-1 positivity in the tumor infiltrating lymphocytes and the PD-L1 positivity in the tumor microenvironment were found to be significant. This shows that PD-1 and PD-L1 are molecules that are effective in the tumor microenvironment as well as physiological interactions. It is important to evaluate the expression of PD-1 and PD-L1 in the determination of patient selection criteria for the use of PD-1 and PD-L1-targeting agents that contribute to treatment in solid tumors and Hodgkin lymphomas. As a result of our study, in order to take into consideration the treatment option targeting PD-1 and PD-L1 in patients with both novo and transformed DLBCL, it was concluded that immunohistochemical method can be used as a cost-effective screening method in the first stage.