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

Abstract

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 naïve 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.