EVALUATION OF PD-1/ PD-L1 EXPRESSION, TUMOR MICROENVIRONMENT AND PROGNOSTIC PROPERTIES IN DIFFUSE LARGE B CELL LYMPHOMA
Project no. 20625 · Status: Kapanmış (Yayın bekleniyor) · 2019
Summary
Diffuse large B cell lymphoma (DLBCL), is classified in mature B cell neoplasms according to WHO classification. The 5 year overall survival is approximately 60-70% with standard chemotherapy regimens. The prognosis of DLBCL patients varies even with the same treatment protocols. Therefore, biomarkers are needed for predicting prognosis and for targeted therapies. In our study, the data of the archival records between the years of 2009-2016 were evaluated in the Department of Pathology, Ege University Faculty of Medicine Hospital. A total of 163 cases, diagnosed as DBBHL, NOS were included in the study. All cases were re-evaluated for the slides of CD3, CD20, BCL-2, BCL-6, MUM1, CD10, MYC, Ki67 markers and presence of EBV infection by EBER-CISH method that were in our archive. Immunohistochemical stainings of PD-L1, PD-1, FOXP3, CD4, CD8, CD68 and CD163 were performed to evaluate the expression of tumor and microenvironment. The median age of the subjects included in the study at the time of diagnosis was 62 years (minimum;13- maximum; 92). Eighty-three (50.9%) of the patients were female and 80 (49.1%) were male. The median follow-up period was 81 months (minimum;1- maximum; 143). Forty of them (24.5%) died and 29 of them (17.8%) had disease progression detected by biopsy or PET / CT. The median overall survival was 115.7 ± 4.2 months. The median value of progression-free survival was 103.8 ± 3.4 months. One-year overall survival rate was 92.4%; three-years 84.6% and the five-years was 80%. One-year progression-free survival was 87.3%; three-years was 77% and the five-years was 73.1%. The increase in the age was found to have a 1.066-fold increased risk for overall survival (p <0.001), and a 1.036-fold increased risk for progression-free survival (p = 0.034). According to Hans algorithm, 101 (62%) of the cases were evaluated in non-GCB / ABC and 62 (38%) were in GCB phenotype. We evaluated microenvironment and PD-1 / PD-L1 expression in tumor cells, which play an important role both in predicting prognostic differences and in identifying patients suitable for immunomodulatory therapies. We did not find a significant correlation in the survival analysis with the FOXP3,CD4,CD8,CD68,CD163 and PD-1/PD-L1 expressions in tumor microenvironment or tumor cells. We found statistically significant results in the analysis of the prognostic significance of the Hans algorithm, bone marrow involvement, serum LDH level, Ki67 proliferation index, and immunohistochemical properties of tumor cells or microenvironment. 73.2% of patients with PD-L1 expression in the tumor were in the ABC subgroup, which is known to have a worse prognosis than GCB subgroup. In addition, Ki67 proliferation index, another parameter that can be evaluated prognostically, was significantly higher in patients with PD-L1 expression in the tumor. Although PD-1, which is the target of immune control point inhibitors, was found to be positive in a small number of tumors, it was found that the risk of progression was increased by 0.359 times with increasing expression rate (p <0.001). Patients with PD-L1 positivity in the microenvironment were significantly more often in the GCB subgroup. Although PD-L1 expression in neoplastic cells was not correlated with survival analysis in DLBCL cases, PD-L1 expression in neoplastic cells may be associated with poor prognosis due to Ki67 proliferation index and ABC type relationship. A detailed understanding of tumor microenvironment and tumor cell interactions will shed light on identifying new therapeutic expansions and developing new therapeutic agents. In order to establish the relationship between tumor, tumor microenvironment and prognostic features, studies in large case series are needed.