Human Effectors of Acute and Chronic GVHD Overexpress CD83 and Predict Mortality

Purpose: Acute and chronic GVHD remain major causes of transplant-related morbidity and mortality (TRM) after allogeneic hematopoietic cell transplantation (alloHCT). We have shown and kill myeloid leukemia cell lines. In this pilot study, we investigate CD83 expression on GVHD effector cells, correlate these discoveries with clinical outcomes, and evaluate critical therapeutic implications for transplant recipients. Experimental Design: CD83 expression was evaluated among cells, and monocytes from patients with/without acute or chronic GVHD (n = 48 for each group), respectively. CD83 expression was correlated with survival, TRM, and relapse after alloHCT. Differential effects of GVHD therapies on CD83 expression was determined. Results: CD83 overexpression on CD4+ T cells correlates with reduced survival , increased TRM. Increased CD83+ B cells and Tfh cells, but not monocytes, are associated with poor posttransplant survival. CD83 CAR T eliminate autoreactive CD83+ B cells isolated from patients with chronic GVHD, without B-cell aplasia as observed with CD19 CAR T. We demonstrate robust CD83 antigen density on human acute myeloid leukemia (AML) , confirm potent antileuke-mic activity of CD83 CART in vivo, without observed myeloablation. Conclusions: CD83 is a promising diagnostic marker of GVHD and warrants further investigation as a therapeutic target of both GVHD and AML relapse after alloHCT.

Automated summary

This study investigates the association between CD83 expression on GVHD effector cells and clinical outcomes after allogeneic hematopoietic cell transplantation. The results show that CD83 overexpression correlates with reduced survival and increased TRM. CD83 CAR T can eliminate autoreactive CD83+ B cells without causing B-cell aplasia. CD83 may serve as a diagnostic marker of GVHD and a therapeutic target for both GVHD and AML relapse after alloHCT.