EVALUATION OF PD-1/ PD-L1 EXPRESSION, TUMOR MICROENVIRONMENT AND PROGNOSTIC FACTORS IN DIFFUSE LARGE B CELL LYMPHOMA


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Basmacı G., Demir D. , Hekimgil M. , Ulusoy Y., Saydam G. , Özsan N.

8th International Congress on Leukemia Lymphoma Myeloma, İstanbul, Turkey, 21 - 22 May 2021, vol.38, no.51, pp.41-42

  • Publication Type: Conference Paper / Full Text
  • Volume: 38
  • City: İstanbul
  • Country: Turkey
  • Page Numbers: pp.41-42

Abstract

Diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS), which is classified in mature B cell neoplasms, constitutes 25-35% of adult non-Hodgkin lymphomas in developed countries. The prognosis of DLBCL patients varies even with the same treatment protocols. Therefore, biomarkers are needed for predicting prognosis and for targeted therapies. Recent studies have shown that tumor microenvironment (TME) plays an important role in cancer development and progression as in DLBCL. Activation of tumor-specific cytotoxic CD8 positive T lymphocytes produce an anti-tumor immune response. CD4 positive and FOXP3 positive regulatory T cells (Treg), myeloid-derived suppressor cells and molecules such as PD-1 and PDL-1, which are effective at the immune control point, have positive inhibitory effects on CD8 positive T cells. CD68 positive tumor-associated macrophages (TAMs) have been reported to contribute to tumor growth and progression by producing growth factors, cytokines, and proteases.

In our study, a total of 163 cases, diagnosed as diffuse large B cell lymphoma, NOS were included in the study. All cases were re-evaluated. Immunohistochemical staining of PD-L1, PD-1, FOXP3, CD4, CD8, CD68 and CD163 were performed to evaluate the expression status of tumor and TME. We evaluated TME and PD-1/PD-L1 expression in tumor cells. 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 TME cells or tumor cells. However, 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 TME. 73.2% of patients with PD-L1 expression in the tumor were in the actived B cell (ABC) subgroup, which is known to have a worse prognosis than germinal center B cell (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 cells. 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). PD-L1 positivity in the TME was significantly higher 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 options and developing new therapeutic agents.

Keywords: PD-1, PD-L1, DBBHL, tumor microenvironment, prognosis