LY-01. Myeloid-derived supressor cells and their suppressive potential after autologous hematopoietic stem cell transplantation in patients with multiple myeloma
Tatyana A. Aristova, Tamara V. Tyrinova, Egor V. Batorov, Vera V. Denisova, Svetlana A. Sizikova, Galina Yu. Ushakova, Ekaterina Y. Shevela, Alexander A. Ostanin, Elena R. Chernykh
Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia
Contact: Dr. Tatyana A. Aristova, phone: +7 (383) 228-57-49, e-mail: firstname.lastname@example.org
Myeloid derived suppressor cells (MDSCs) represent a heterogeneous population of myeloid derived cells, which includes early (E-MDSC; Lin–HLA-DR–CD33+), neutrophils and polymorphonucler myeloid-derived (PMN-MDSC; Lin–HLA-DR–CD66b+), and mature MDSCs (M-MDSC; CD14+HLA-DRlow/–), which, through various mechanisms of immunosuppression, are able to participate in the pathogenesis of multiple myeloma (MM) leading to tumor progression and antitumor therapy resistance mechanisms formation. We investigated the circulating MDSCs dynamics and arginase-1 suppressor molecule expression in patients with MM in the first 12 months after autologous hematopoietic stem cell transplantation (auto-HSCT) and the relationship between the MDSC content and auto-HSCT outcomes.
Materials and methods
The study included 44 patients with MM who underwent auto-HSCT. The counts of granulocytic (G-MDSCs; Lin–HLA-DR–CD33+CD66b+), monocytic (М-MDSCs; CD14+HLA-DRlow/–) and early MDSCs (Lin–HLA-DR–CD33+CD66b–) were assessed by flow cytometry.
After the patients underwent auto-HSCT, the relative amount of circulating M-MDSC (pU=0.038) and PMN-MDSC (pU=0.003) statistically significantly increased by the time engraftment. The absolute PMN-MDSC count also increased significantly (pU=0.005). Six months after auto-HSCT, the circulating М-MDSC and PMN-MDSC proportion significantly decreased (pU=0.007 and pU=0.024, respectively) to pre-transplant values and remained similar at 12 months after auto-HSCT. The relative and absolute number of E-MDSC at the time of engraftment, on the contrary, was reduced in comparison to similar values prior to auto- HSCT (for absolute values, it was statistically significant; pU=0.004). The circulating E-MDSC proportion among MNCs remained the same during the entire 12-month post-transplant period. While absolute number of MNCs increased, the absolute E-MDSC content also increased and was significantly higher 12 months after auto-HSCT compared to the period of engraftment (pU=0.032).
The analysis of relapse-free survival based on the median relative PMN-MDS value at engraftment (Me, 0.17%) showed that, in patients with PMN-MDSC counts of >0.17%, the proportion of patients free of early relapse was 94±6%. Meanwhile, in cases of PMN-MDSC ≤0.17%, only 67±11% patients were relapse-free, thus being significantly lower (p=0.049). In the group of patients with early recurrence, the proportion of M-MDSC expressing arginase -1 at the time of recovery from leukopenia showed a trend to lower values compared to the same index in the group of patients who maintained a response over the first 12 months of the post-transplant period.
The association of early MM recurrence after auto-HSCT with lower content of PMN-MDSC and reduced counts of arginase-1+ M-MDSC at the stage of recovery from leukopenia may suggest that MDSC is involved into restriction of homeostatic cell proliferation as a prerequisite for more effective immune reconstitution.
Myeloid suppressors, autologous hematopoietic stem cell transplantation, multiple myeloma, suppressor molecules, arginase-1.