Evalution of microenvironment profile in hodgkin's lymphoma

Purpose: Hodgkin's Lymphoma is a curable malignant disease. However, in 15-20% of patients, the disease recurs or becomes refractory. RS cells are rare in histopathological specimens and initiate the malignancy. There is dense microenvironment around it. However, the role of T and B lymphocytes that constitute the microenvironment has not been exactly defined. Significant clues have been found between prognosis and expression of Programmed Death-1 (PD-1), Programmed Death Ligand (PD-L1), GRB and Forkhead Box3 (FOXP3) which are regulating T and B lymphocyte functions. Patients and Methods: Sixty-two patients diagnosed with Hodgkin's Lymphoma treated at the Department of Oncology in Çukurova University included in the study. Clinical, demographic and laboratory data of the patients were reviewed. PD-1, PDL-1, FOXP-3 and Granzim B were studied with appropriate antibodies immunohistochemically. Expression analysis performed on tumor cell and microenvironment separately and compared with known prognostic parameters. Statistical analysis performed with SPSS 22.0 software programs. p value <0.05 was considered significant. Results: Age (p=0,05), stage 4 disease (p=0,01), initial response to treatment (p=0,03), hypoalbuminemia (p=0,01), lymphocyte count <1000/mm³, neutrophil/lymphocyte ratio ≤3,9 (p=0,009), leucocyte/lymphocyte ratio ≤3,9 (p=0,01), B symptom (p=0,02) and IPS-3 score (p=0,03) were found to be associated with event free survival. PD-1 at RS was found to be positive in only one patient. PD-1 staining in microinvironment was not found to be associated with event free survival. Staining for PD-L1 neither in RS-cell nor microenvironment were associated with survival. Non-specific staining for FOXP3 was detected in 36 cases. Intense staining of granzyme B at RS cells was found to be associated with event free survival. Intense staining for granzyme B was found in in only two cases statistical analyses was not performed. Granzim B staining at microenvironment was not associated with survival. There was no survival difference between simulaneous PD-L1 staining in RS cells and microenvironment, (p=0,06). In addition to the known prognostic parameters and scores in HL, LLO and IPS-4 score were found to be useful. None of the biomarkers determined in this study were found associated with survival. However, more studies, with larger patient groups may provide more precise future treatment approaches. Key Words: Hodgkin's Lymphoma, microenvironment, PD-1, PDL-1, FOXP-3, Granzyme B