Detection of senescent CD8+ T-lymphocyte in newly diagnosed and relapsed/refractory multiple myeloma using CD28 and CD57

Abstract

BACKGROUND: Multiple myeloma is a clonal B-cell malignancy characterized by proliferation of plasma cells that secrete a complete and/or partial monoclonal immunoglobulin protein. It induces dysfunction of cytotoxic T cells that may be responsible for immune evasion and therapeutical failure of immunotherapies. T cells during senescence tend to lose co-stimulatory molecules such as CD27 and CD28 while expressing killer cell lectin-like receptor subfamily G (KLRG-1) and CD57. Therefore, enhanced knowledge about the actual status of T cells in myeloma patients is needed. Objectives: The aims of this study were to detect the senescent cytotoxic T-cell (CD8+) in patients with refractory/resistance multiple myeloma, and to compare it with newly diagnosed multiple myeloma patients, and their implications for cellular therapies. MATERIALS AND METHODS: This is a cross sectional study performed, from January to October 2021. Sixty multiple myeloma patients were sequentially chosen, thirty of them were newly diagnosed patients and another thirty were relapse/refractory who progress after receiving 2 lines of chemotherapy containing bortezomib and immunomodulators. And/or patients progressing after autologous stem cell transplantation. Seventeen apparently healthy age and gender matched adults were enrolled as a control group. Multicolor flow cytometry was utilized for the analyses of surface molecules CD 28 and CD57 on CD 8 positive T-lymphocyte using peripheral blood, subsequently the percentage of T cells senescent were estimate in CD 8+ T cells with CD28- and CD57+. Results: The mean percentage of senescent CD8 positive T lymphocyte (negative CD28 and positive CD57) were significantly higher in multiple myeloma patients than control (P<0.001). There was no statistically significant difference in percentage of CD8+ T cells between newly diagnosed multiple myeloma and relapsed /refractory cases. However higher percentage of senescent T cells was found in relapsed cases. No significant correlation was found between percentage of CD8 +T cells and patients age, or duration of disease. Conclusion: Percentage of senescent CD 8+ T cells with CD28- and CD 57+were significantly higher in MM patients compared to healthy controls. Percentage of senescent CD 8+ T cells with CD28- and CD 57+were lower in newly diagnosed MM patients compared to relapsed patients but the difference was statistically not significant