Table 3 Impact of interventional... | American Society of Hematology

Table 3

Impact of interventional strategies on DCs and outcome in experimental HSCT

Mechanism	Therapy	GVHD model; treatment	Effect on DCs*	Effect on GVHD	Reference
HDAC inhibition	SAHA or ITF2357	MHC-mismatched BALB/c → B6;	TNF-α, IL-12, and IL-6 secretion ↓	Survival ↑	104
		Host type DCs pretreated with HDAC inhibitor infused days −1, 0, and 2	CD40/CD80/CD86 expression ↓	Clinical score ↓
			Allogeneic T-cell proliferation ↓ (in vitro/in vivo)	Serum TNF-α ↓
				Preserved GVL

Proteasome inhibition	Bortezomib	MHC-mismatched BALB/c → B6;	Response to maturation signals ↓	Survival ↑ with early treatment	108
		Early (days 0-2) versus late (days 6-8) treatment	MHC class II, CD40/CD80/CD83/CD86 expression ↓	Survival ↓ with late treatment
			Apoptosis ↑	Preserved GVL
			Allogeneic T-cell proliferation ↓

NF-κB inhibition	RelB^−/− BM chimera recipients	MHC-mismatched BALB/c → B6	CD11c^hi DCs (cDCs) ↓	Survival ↑	109
			CD40/CD80/CD86 expression unchanged	Clinical score ↓
			IL-12, IL-6, TNF-α secretion ↓ (after CD40L)
			CD4⁺ T-cell proliferation (in vitro/vivo); cytokine secretion ↓ (in vitro)
			No difference PDCA-1⁺ DCs (pDCs), T_reg (in vivo)
	RelB^−/− BM chimera donor	MHC-mismatched B6 → B6D2F1		Late (> 3 wks) survival ↑ and clinical score ↓

Anti-CD83	Polyclonal Ab	Hu SCID; day 0		Survival ↑	110
				Preserved engraftment and GVL

Mechanism	Therapy	GVHD model; treatment	Effect on DCs*	Effect on GVHD	Reference
HDAC inhibition	SAHA or ITF2357	MHC-mismatched BALB/c → B6;	TNF-α, IL-12, and IL-6 secretion ↓	Survival ↑	104
		Host type DCs pretreated with HDAC inhibitor infused days −1, 0, and 2	CD40/CD80/CD86 expression ↓	Clinical score ↓
			Allogeneic T-cell proliferation ↓ (in vitro/in vivo)	Serum TNF-α ↓
				Preserved GVL

Proteasome inhibition	Bortezomib	MHC-mismatched BALB/c → B6;	Response to maturation signals ↓	Survival ↑ with early treatment	108
		Early (days 0-2) versus late (days 6-8) treatment	MHC class II, CD40/CD80/CD83/CD86 expression ↓	Survival ↓ with late treatment
			Apoptosis ↑	Preserved GVL
			Allogeneic T-cell proliferation ↓

NF-κB inhibition	RelB^−/− BM chimera recipients	MHC-mismatched BALB/c → B6	CD11c^hi DCs (cDCs) ↓	Survival ↑	109
			CD40/CD80/CD86 expression unchanged	Clinical score ↓
			IL-12, IL-6, TNF-α secretion ↓ (after CD40L)
			CD4⁺ T-cell proliferation (in vitro/vivo); cytokine secretion ↓ (in vitro)
			No difference PDCA-1⁺ DCs (pDCs), T_reg (in vivo)
	RelB^−/− BM chimera donor	MHC-mismatched B6 → B6D2F1		Late (> 3 wks) survival ↑ and clinical score ↓

Anti-CD83	Polyclonal Ab	Hu SCID; day 0		Survival ↑	110
				Preserved engraftment and GVL

Hu SCID indicates human severe-combined immunodeficiency.

In vitro unless otherwise indicated.