Relevance of Polymorphic KIR and HLA Class I Genes in NK-Cell-Based Immunotherapies for Adult Leukemic Patients

Simple Summary Immunotherapies are promising approaches to curing different acute leukemias. Natural killer (NK) cells are lymphocytes that are efficient in the elimination of leukemic cells. NK-cell-based immunotherapies are particularly attractive, but the landscape of the heterogeneity of NK cells must be deciphered. This review provides an overview of the polymorphic KIR and HLA class I genes that modulate the NK cell repertoire and how these markers can improve the outcomes of patients with acute leukemia. A better knowledge of these genetic markers that are linked to NK cell subsets that are efficient against hematological diseases will optimize hematopoietic stem-cell donor selection and NK immunotherapy design. Since the mid-1990s, the biology and functions of natural killer (NK) cells have been deeply investigated in healthy individuals and in people with diseases. These effector cells play a particularly crucial role after allogeneic hematopoietic stem-cell transplantation (HSCT) through their graft-versus-leukemia (GvL) effect, which is mainly mediated through polymorphic killer-cell immunoglobulin-like receptors (KIRs) and their cognates, HLA class I ligands. In this review, we present how KIRs and HLA class I ligands modulate the structural formation and the functional education of NK cells. In particular, we decipher the current knowledge about the extent of KIR and HLA class I gene polymorphisms, as well as their expression, interaction, and functional impact on the KIR+ NK cell repertoire in a physiological context and in a leukemic context. In addition, we present the impact of NK cell alloreactivity on the outcomes of HSCT in adult patients with acute leukemia, as well as a description of genetic models of KIRs and NK cell reconstitution, with a focus on emergent T-cell-repleted haplo-identical HSCT using cyclosphosphamide post-grafting (haplo-PTCy). Then, we document how the immunogenetics of KIR/HLA and the immunobiology of NK cells could improve the relapse incidence after haplo-PTCy. Ultimately, we review the emerging NK-cell-based immunotherapies for leukemic patients in addition to HSCT.

Automated summary

Immunotherapies show promise in treating acute leukemias, with NK cells playing a crucial role in eliminating leukemic cells. Understanding the impact of genetic markers like KIR and HLA on NK cell subsets can improve patient outcomes. Investigating the immunogenetics of KIR/HLA and the immunobiology of NK cells may lead to improved treatments for leukemic patients undergoing HSCT.