Advances and challenges in immunotherapy for solid organ and hematopoietic stem cell transplantation

Abstract

Although major advances have been made in hematopoietic stem cell transplantation (HSCT) and solid organ transplantation in the last 50 years, big challenges remain. This Review outlines the current immunological limitations for HSCT and solid organ transplantation, and discusses new immune-modulating therapies in clinical trials and under pre-clinical development that may allow these obstacles to be overcome.

Peri-alloHCT IL-33 administration expands recipient T-regulatory cells that protect mice against acute GVHD

“…47 Effectively increasing the Treg-to-Teffector ratio is understood to be crucial for Treg control of alloimmune responses in the setting of transplantation and GVHD. 70,72 Increasing Tregs to adequate protective numbers via adoptive transfer suppresses the alloimmune responses underlying GVHD and has shown therapeutic efficacy in preclinical rodent studies and early-stage clinical trials. For instance, adoptive transfer of ex vivo-expanded Tregs reduced grade II-IV GVHD.…”

Systems analysis uncovers inflammatory Th/Tc17-driven modules during acute GVHD in monkey and human T cells

“…This short-term success has relied on the use of broadly active, nontargeted immune suppression, which has succeeded in controlling very early immune activation. 1 In solid-organ transplantation, this results in high 1-year survival times for many transplanted organs (eg, 90% 1-year survival for renal transplants) but with the ultimate occurrence of immune-mediated rejection in the vast majority of patients (with a half-life of ;10 years for renal transplants 2 ). In HCT, similar immunosuppressive strategies result in most patients engrafting, but with up to 70% of patients ultimately developing acute graft-versushost disease (GVHD), with the most severe cases being untreatable and lethal.…”

Programmed death ligand-1 expression on donor T cells drives graft-versus-host disease lethality

“…Current approaches to prevent or treat GVHD focus on blocking T cell activation or the proinflammatory products of activated T cells using immunosuppressive drugs such as calcineurin inhibitors, mycophenolate mofetil, and corticosteroids. Many new drugs in various stages of development aim to more specifically target selective T cell functions or activated T cells (3), including agents designed to block T cell costimulatory pathways such as CD28, CD154, and ICOS.…”