Expression features of antigens involved in the formation of immunological synapse in splenic marginal zone lymphoma
Authors: Badmazhapova D. S. , Galtseva I. V. , Zvonkov E. E. , Davydova Yu. O. , Kapranov M. M. , Moiseeva T. N. , Kovrigina A. M. , Julhakyan U. L. , Danishyan K. I. , Sabirov K. R. , Parovichnikova E. N. , Savchenko V. G. 
Published: December 2020

Background. Splenic marginal zone lymphoma (SMZL) is an indolent non-Hodgkin’s B-cell lymphoma. It presents morphologically by mature lymphoid B-cells. They conform to these immunological characteristics of marginal zone lymphocytes from secondary follicles. The tumor B-cells of SMZL do not have specific markers of immunophenotype and requires the exclusion of other non-Hodgkin’s B-cell lymphomas. There is an annual increase in the incidence of SMZL. There are refractory forms and progressive course of the SMZL. There is a huge variety of the mechanisms of evading tumor cells from immunological control. Unlike solid tumors, B-lymphoproliferative diseases are characterized by the expression of HLA I/II and co-stimulatory molecules (CD80 and CD86). Therefore, tumor B-lymphocytes can act as antigen-presenting cells (APC) for T lymphocytes. The T-cell immune response is known to play an important role in antitumor control. It is known that effective activation of T-lymphocytes requires the formation of an immunological synapse and the presence of two activation signals (antigen recognition and co-stimulation of CD28-CD80/86). According to the modern concept of tumor development, there is a gradual selection of tumor clones. As a result, only tumor cells that are invisible to the immune system remain. Mechanisms of evasion of tumor B-cells of SMZL from immune surveillance are currently not fully understood and are being actively studied.

Objective: to study the expression features of antigens involved in the formation of immunological synapse in patients with SMZL in peripheral blood.

Materials and methods. The study includes 10 primary SMZL patients; all patients have stage IV according to the Ann Arbor classification. Splenectomy was performed for all patients as a first stage of treatment. Two patients had progression of SMZL after splenectomy, which required chemotherapy. The control group included 25 healthy donors. Peripheral blood was used as a material for analysis. The study was conducted on a 6-color BD FACS Canto II flow cytometer (BD Biosciences, USA) immediately after diagnosis.

Results. Tumor B-cells of SMZL are different from B-cells of healthy donors with a greater proportion of CD80+, FAS+, PD-1+-cells, which may correspond to activated B-cells. The proportion of CD4+PD-1+ and CD8+PD-1+ T-cells in patients with SMZL was higher in comparison with the control group. There was a large proportion of T-cells expressing PD-1 in the group of patients with SMZL progression after splenectomy in comparison with the group of patients with indolent course of SMZL. Conclusion. Thereby, tumor B-cells of the SMZL retains the features of non-tumor analogues. The most significant mechanism for evading immune surveillance in an SMZL is inhibition of the T-cell immunity via the PD-1–PD-L1 pathway. The most pronounced inhibition of T-cell immunity causes an uncontrolled tumor process.