Table 1.

Summary of clinical findings and mechanisms for each MDSC immunophenotype.

MDSC Immunophenotype	Clinical Finding	Mechanism	Reference
CD11clow, MHCIIlow, F4/80int	Exposure to inflammasome-stimulating mediators negates the suppressive function of cultured murine and human-derived MDSCs	MDSC-IL13 were activated for NLRP3 or AIM2 inflammasomes using either LPS plus ATP or LPS plus poly(dT) transfection	Koehn et al. [46]
Murine MDSC-IL13s	Inhibition of the inflammasome pathway resulted in maintained MDSC function and improved survival after HSCT in the aGVHD model	Inflammasome activation was reduced via P2x7 knockout (KO) or suppression of ATP binding to the receptor (exhibited with extracellular ATP depletion via apyrase and pharmacologically via administration of A-438079, a highly specific P2x7R inhibitor)	Koehn et al. [47]
G-MDSCs expressing CD11b+Gr-1+, Ly-6ClowLy-6G+ and M-MDSCs expressing CD11b+Gr-1+, Ly-6ChighLy-6G−	MDSCs prevented GVHD-induced death and diminished histologic GVHD	MDSCs induce Th2, while anti-tumor cytotoxicity of alloantigen-specific T cells was preserved	Messmann et al. [48]
H-2Kb+CD11b+Gr-1+	Addition of functional MDSCs in donor graft-attenuated GVHD, while the removal of MDSCs in vivo exacerbated GVHD. MDSCs derived from recipients with GVHD demonstrated induced suppressive potency compared with those from recipients without GVHD. Tumor relapse allowed progressive accumulation of MDSCs in the peripheral blood and spleens of recipients after allo-HCT. Thus, monitoring blood MDSCs may predict relapse	MDSCs suppress alloreactive T cell responses	Wang et al. [49]
CD115+Gr-1+F4/80+	MDSCs effectively attenuated GVHD but did not significantly compromise GVL effects	MDSC demonstrated cytolytic activities against allogeneic leukemia cells via induction of NKG2D+ CD8 T cells, whereas suppressed GVHD through upregulation of T Regs	Zhang et al. [50]
HLA-DR−/lowCD33+CD16- cells	eMDSCs prevented GVHD in humanized mouse model and suppressed the occurrence of grade II-IV aGVHD in allo-HCT patients	eMDSCs are implicated in T Reg upregulation and polarization of T cells from Th1/Th17 to Th2	Wang et al. [51]
CD11bhighGr-1low	MDSCs induce IL-10-producing T Reg that inhibit GVHD through MHC class II restriction	Indirect presentation of host (H-2d) peptides throughMHC class II donor molecules	McDonald et al. [43]
CD11b+Gr-1+	MDSCs inhibit T cell mediated immunoreactivity and GVHD	Decreased number and dysfunction of T cells, the presence of enriched MSCs and/or the increased IL-10, IL-6 cytokine secretion	Morecki et al. [52]
CD11b+Gr-1+	Suppression of acute GVHD by inhibiting alloreactive donor T cell expansion	MDSC suppress GVHD via an IDO-independent manner	Joo et al. [53]
CD11b+Gr-1+	MDSCs suppress allogeneic T cell responses, both in vitro and in vivo	MDSCs triggered arginase-1 activity, which depleted T cell L-arginine	Highfill et al. [54]
CD11bintCD34+	CD34+ M-MDSCs producing NO mediate apoptosis in alloreactive T cell	CD34+ monocytes mobilized with G-CSF require T cell–mediated IFN-γ to yield NO that attenuates T cell activation and proliferation	D’Aveni et al. [55]
CD11b+Gr-1+	MyD88 signaling in donor BM cells demonstrated a protective role via allowing the amplification of MDSCs derived from the donor TCD-BM	GVHD was induced with T cell-depleted BM (TCD-BM) collected from MyD88KO C57BL/6 (B6) mice and T cells collected from WT B6 mice	Lim et al. [56]
M-MDSCs (CD11b+ Ly-6GnegLy-6Chigh) and G-MDSCs (CD11b+Ly-6Gpos Ly-6Clow)	RAPA can significantly alleviate acute graft-versus-host disease	RAPA enhances the immunosuppressive function of PMN-MDSCs via induction of ARG1 and iNOS and stimulation of regulatory T cells in vivo	Lin et al. [57]
M-MDSCs (CD11b+ Ly-6GnegLy-6Chigh) and G-MDSCs (CD11b+Ly-6Gpos Ly-6Clow)	RAPA treatment induced the immunosuppressive role of MDSCs and inhibited GVHD, while GVT effect was maintained	MDSCs from RAPA-treated mice showed increased immunosuppressive potential, which was primarily iNOS-dependent	Scheurer et al. [58]
HLA-DR+CD33+CD14+	Treatment with gal-9 inhibited GVHD	Treatment with gal-9 increased G-MDSCs through stimulations of iNOS and ARG1	Yin et al. [59]
CD11c–CD11b + and Gr-1 +	Infusion of MDSCs and T Regs inhibited aGVHD	Combined treatment modulated differentiation of allogeneic T cells toward T Regs and IL-10-secreting regulatory B cells	Park et al. [60]

HCT, hematopoietic cell transplantation; RAPA, rapamycin; aGVHD, graft-versus-host disease; ARG1, arginase 1; iNOS, inducible nitric oxide synthase.