Separation of GVL from GVHD -location, location, location

Front Immunol. 2023 Dec 5:14:1296663. doi: 10.3389/fimmu.2023.1296663. eCollection 2023.

Abstract

Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for various hematologic malignancies. However, alloimmune response is a double-edged sword that mediates both beneficial graft-versus-leukemia (GVL) effects and harmful graft-versus-host disease (GVHD). Separation of GVL effects from GVHD has been a topic of intense research to improve transplant outcomes, but reliable clinical strategies have not yet been established. Target tissues of acute GVHD are the skin, liver, and intestine, while leukemic stem cells reside in the bone marrow. Tissue specific effector T-cell migration is determined by a combination of inflammatory and chemotactic signals that interact with specific receptors on T cells. Specific inhibition of donor T cell migration to GVHD target tissues while preserving migration to the bone marrow may represent a novel strategy to separate GVL from GVHD. Furthermore, tissue specific GVHD therapy, promoting tissue tolerance, and targeting of the tumor immune microenvironment may also help to separate GVHD and GVL.

Keywords: graft-versus-host disease; graft-versus-leukemia; intestine; tissue tolerance; tumor immune environment.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Graft vs Host Disease* / etiology
  • Hematologic Neoplasms* / therapy
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Immune Tolerance
  • T-Lymphocytes
  • Tumor Microenvironment

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by JSPS KAKENHI (21H02944 and 23K18296 to TT, 21K08409 to DH).