Frontiers in Immunology (May 2019)
Dynamics of Expression of Programmed Cell Death Protein-1 (PD-1) on T Cells After Allogeneic Hematopoietic Stem Cell Transplantation
Abstract
Immune exhaustion contributes to treatment failure after allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies. Immune checkpoint blockade, including programmed cell death protein-1 (PD-1) blockade, is a promising strategy to improve the antitumor effect of allogeneic HSCT with high rates of response reported in patients treated for disease relapse. However, severe and sometimes fatal Graft- vs.-Host-Disease (GvHD) has been reported as a complication. Little is known about the dynamics of PD-1 expression on immune effector cells after allogeneic HSCT. In the present study, we analyzed PD-1 expression on T cell subpopulations isolated from 105 allogeneic HSCT recipients. Our analysis revealed a significant increase in proportions of PD-1-expressing CD4 and CD8 T cells early after allogeneic HSCT followed by a progressive normalization of PD-1 expression at CD8 but not CD4 T cell surface. Analysis of co-expression of two other exhaustion markers, 2B4 and CD160, revealed a preferential expansion of PD-1-single positive cells. Moreover, the analysis of granzyme B and perforin expression in PD-1+ and PD-1- CD8 T cells from HSCT recipients did not reveal any impairment in cytotoxic molecules production by PD-1-expressing CD8 T cells. Analyzing the association between clinical factors and the expression of PD-1 on T cells, we identified the use of in vivo and/or ex vivo T-cell depletion as the factor most strongly associated with elevated PD-1 levels on T cells. Our results extend our knowledge of the regulation of PD-1 expression at T cell surface after allogeneic HSCT, a crucial information for the optimization of post-transplantation PD-1 blocking therapies.
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