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T-cell sub group analysis and T-cell exhaustion after autologous stem cell transplantation in lymphoma patients

2022
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Advisor: Doç. Dr. Elif Birtaş Ateşoğlu

Abstract (EN)

The composition and function of cells regenerated in the bone marrow after autologous stem cell transplantation (ASCT) are among the factors affecting the success of the treatment. One of the defined concepts associated with dysfunction is T cell exhaustion. This concept is characterized by the loss of ability of the T cells to secrete cytokines and proliferate as a result of chronic antigen exposure and the expression of multiple inhibitory receptors. In this study, it is aimed to evaluate the change of T cell sub groups and T cell exhaustion of 32 lymphoma patients, by flow cytometry analysis performed on peripheral blood samples pre-ASCT and on the first, third and sixth months post-ASCT. Inhibitory receptor (PD-1, LAG-3, CTLA-4) expressions were analyzed to evaluate exhaustion. CD57 + CD28 - T cells were examined to demonstrate senescence. As a result of the study, the number of CD4 + T cells is found to be significantly low after transplantation and a statistically significant decrease is observed on the CD4 + /CD8 + ratio. Before transplantation, T cells of the patients showed significant aging senescence, and it was noted that this situation persisted after transplantation. Both single and multiple expressions of LAG-3 and PD-1 are found to be high before transplantation. It is noticed that the expression of these receptors decreased after transplantation. However, it was detected that LAG-3 expression is increased on the 3 rd month and PD-1 expression is increased on the 6 th month after transplantation. These changes were more evident for the relapsed patients, and especially the expressions of inhibitory receptors were significantly higher at the first month post-transplant when compared to non-relapsed patients. Our results show that both the composition and functional properties of T cells change after ASCT. High levels of inhibitory receptors and senescence markers of relapsed patients suggest that these molecules are predictive in post-transplant disease prognosis. Studying these molecules in a larger patient population and elucidating bone marrow immunomodulation will pave the way for appropriate interventions in the treatment by identifying the risky disease group.

Author

Kayra Somay

Institution

How to Cite

Kayra Somay (Medical Specialty Thesis). T-cell sub group analysis and T-cell exhaustion after autologous stem cell transplantation in lymphoma patients, 2022, Koç University.

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