Contributions
Abstract: PB2480
Type: Publication Only
Background
Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immature, immunosuppressive cells that play a role in cancer induction, progression and immune evasion. Two major MDSC subsets exist: polymorphonuclear (PMN-MDSC) and monocytic MDSC (M-MDSC). Recent studies indicated that the immune reconstitution after autologous hematopoietic stem cell transplantation (ASCT) is associated with outcome. Since MDSC are immunosuppressive cells, we hypothesize that they play a role in the immune reconstitution and outcome after ASCT.
Aims
The aim of this study is to define the presence and function of MDSC in ASCT. Therefore, we will phenotypically and functionally analyze different MDSC subsets. Since the content of the peripheral blood stem cell (PBSC) graft is less defined, we will analyze MDSC and other immune cells in the PBSC graft. In addition, the immune reconstitution after ASCT will be studied in relation to the amount of MDSC infused and the kinetics of MDSC after ASCT will be assessed.
Methods
Flow cytometry is used to study the presence of MDSC in peripheral blood mononuclear cells (PBMC) and in the PBSC graft of multiple myeloma and lymphoma patients, undergoing ASCT.
Results
The kinetics of MDSC levels are similar between M-MDSC and PMN-MDSC during the transplantation period. MDSC levels in PBMC and in the PBSC graft increased after G-CSF mobilization, together with an increased IL-4Rα expression on MDSC. At the time of ASCT, following high-dose chemotherapy, MDSC levels had decreased. After ASCT, MDSC levels recovered again. Interestingly, the PMN-MDSC/M-MDSC ratio was lower in the PBSC graft, compared to PBMC.
Conclusion
Recent findings have provided proof that immune reconstitution plays a key role in the therapeutic effect of ASCT. Since MDSC are known to be immunosuppressive cells that accumulate after G-CSF mobilization protocols, they may play a role in the immune reconstitution and outcome after ASCT. Indeed, after G-CSF mobilization, both M-MDSC and PMN-levels were increased. Interestingly, IL-4Rα expression on MDSC increased, suggesting a higher immunosuppressive activity of MDSC. In addition, the PMN-MDSC/M-MDSC ratio was decreased in the PBSC graft as compared to PBMC. This may suggest that in the PBSC graft less PMN-MDSC and/or more M-MDSC, which are considered to be the most immunosuppressive population, are present. Further ex vivo assays will be performed to study the immunosuppressive capacity of MDSC in PBMC and in the PBSC graft. Moreover, more patients will be included to further study the role of MDSC in ASCT.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Autologous hematopoietic stem cell transplantation, Immunosuppression
Abstract: PB2480
Type: Publication Only
Background
Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immature, immunosuppressive cells that play a role in cancer induction, progression and immune evasion. Two major MDSC subsets exist: polymorphonuclear (PMN-MDSC) and monocytic MDSC (M-MDSC). Recent studies indicated that the immune reconstitution after autologous hematopoietic stem cell transplantation (ASCT) is associated with outcome. Since MDSC are immunosuppressive cells, we hypothesize that they play a role in the immune reconstitution and outcome after ASCT.
Aims
The aim of this study is to define the presence and function of MDSC in ASCT. Therefore, we will phenotypically and functionally analyze different MDSC subsets. Since the content of the peripheral blood stem cell (PBSC) graft is less defined, we will analyze MDSC and other immune cells in the PBSC graft. In addition, the immune reconstitution after ASCT will be studied in relation to the amount of MDSC infused and the kinetics of MDSC after ASCT will be assessed.
Methods
Flow cytometry is used to study the presence of MDSC in peripheral blood mononuclear cells (PBMC) and in the PBSC graft of multiple myeloma and lymphoma patients, undergoing ASCT.
Results
The kinetics of MDSC levels are similar between M-MDSC and PMN-MDSC during the transplantation period. MDSC levels in PBMC and in the PBSC graft increased after G-CSF mobilization, together with an increased IL-4Rα expression on MDSC. At the time of ASCT, following high-dose chemotherapy, MDSC levels had decreased. After ASCT, MDSC levels recovered again. Interestingly, the PMN-MDSC/M-MDSC ratio was lower in the PBSC graft, compared to PBMC.
Conclusion
Recent findings have provided proof that immune reconstitution plays a key role in the therapeutic effect of ASCT. Since MDSC are known to be immunosuppressive cells that accumulate after G-CSF mobilization protocols, they may play a role in the immune reconstitution and outcome after ASCT. Indeed, after G-CSF mobilization, both M-MDSC and PMN-levels were increased. Interestingly, IL-4Rα expression on MDSC increased, suggesting a higher immunosuppressive activity of MDSC. In addition, the PMN-MDSC/M-MDSC ratio was decreased in the PBSC graft as compared to PBMC. This may suggest that in the PBSC graft less PMN-MDSC and/or more M-MDSC, which are considered to be the most immunosuppressive population, are present. Further ex vivo assays will be performed to study the immunosuppressive capacity of MDSC in PBMC and in the PBSC graft. Moreover, more patients will be included to further study the role of MDSC in ASCT.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Autologous hematopoietic stem cell transplantation, Immunosuppression