T cell subgroup analysis and T cell exhaustion after autologous stem cell transplantation in lymphoma patients

Background: Autologous stem cell transplantation (ASCT) is a common treatment option for relapsed/refractory (R/R) lymphomas and it is considered standard of care as primary consolidation therapy for some types of Non-Hodgkin Lymphomas (NHL). Although ASCT benefits patients by allowing cytoreduction with intensive chemotherapy and reconstituting with stem cells, the effects of immunological changes in T cell subgroups after ASCT are still poorly understood. Objectives: We evaluated changes in frequencies of T cell subsets and T cells expressing some of the exhaustion markers (such as LAG-3 and PD-1) from peripheral blood samples before and after ASCT to investigate bone marrow reconstruction and whether exhaustion predicts relapse. Study design: Blood samples were collected on the day before conditioning and at the 1st, 3rd, and 6th months post-ASCT. Flow cytometry analysis was conducted to examine T cell subgroup composition and exhaustion markers, including PD-1 and LAG-3. Additionally, functional analysis was performed using assays for IFN-g and TNF-a production. Furthermore, a CSFE proliferation assay was utilized to assess proliferation capacity. Results: In our data set, dominant cells post-transplantation were memory cells, as the na & iuml;ve cell population did not recover for 6 months. Both single and combined expressions of LAG-3 and PD-1 were found to be high before transplantation, and decreased after transplantation. However, LAG-3 and PD-1 expression increased in the 3rd and 6th month after transplantation respectively. These changes were more evident for the relapsed patients when compared to non-relapsed patients within 3 months follow-up time. Notably, the expression of inhibitory receptors in the relapsed patients was significantly higher at the first month post-transplantation. CD107a+ cytotoxic T lymphocytes (CTL), IFN-g+, TNF-a.+ CTL and T helper lymphocyte (THL) populations significantly decreased in relapsed patients 3rd month after transplantation. Decreased proliferation capacities of CTLs and THLs were also observed in these patients. Conclusion: These results suggest that increased surface PD-1 and LAG-3 expressions along with functional decline after 3 months of ASCT can be used as prognostic data about the relapse status of transplant patients.