NK Cells and γδT Cells for Relapse Protection after Allogeneic Hematopoietic Cell Transplantation (HCT)

Purpose of Review: The outcome of allogeneic stem cell transplantation (allo-HCT) is still compromised by relapse and complications. NK cells and γδT cells, effectors that both function through MHC-unrestricted mechanisms, can target transformed and infected cells without inducing graft-versus-host disease (GVHD). Allo-HCT platforms based on CD34+ selection or αβ-TCR depletion result in low grades of GVHD, early immune reconstitution (IR) of NK and γδT cells and minimal usage of GVHD prophylaxis. In this review we will discuss strategies to retain and expand the quantity, diversity, and functionality of these reconstituting innate cell types. Recent Findings: Bisphosphonates, IL-15 cytokine administration, specific antibodies, checkpoint inhibitors, and (CMV based) vaccination are currently being evaluated to enhance IR. All these approaches have shown to potentially enhance both NK and γδT cell immuno-repertoires. Summary: Rapidly accumulating data linking innate biology to proposed clinical immune interventions will give unique opportunities to unravel shared pathways which determine the graft-versus-tumor effects of NK and γδT cells.