Translational potential of γδ T cells in hematologic diseases: from immunobiology to therapeutic innovation
Year: 2026
Type: article
Abstract: Hematologic disorders, including malignant and autoimmune conditions, present persistent clinical challenges characterized by relapse, treatment resistance, and profound immune dysregulation. While conventional immunotherapies have advanced, their efficacy is frequently limited by HLA downregulation and effector T cell exhaustion. In this context, γδ T cells offer a promising therapeutic alternative. Recognizing antigens independently of MHC restriction, γδ T cells possess intrinsic tissue-homing capabilities and exhibit dual cytotoxic and immunoregulatory functions. These properties make them highly suitable candidates for allogeneic, “off-the-shelf” cellular therapies where αβ T cells face alloreactive limitations. This review systematically synthesizes the immunobiology of γδ T cells, exploring the functional heterogeneity of specific subsets and their regulation within the tumor microenvironment (TME). We critically evaluate recent preclinical and clinical evidence supporting adoptive transfer, CAR-γδ T strategies, and combination regimens across acute leukemias, lymphomas, multiple myeloma, and immune cytopenias. Furthermore, we address critical translational barriers—including in vivo persistence, subset exhaustion, and manufacturing variability—and discuss rational engineering strategies, metabolic preconditioning, and epigenetic modulation as solutions. Ultimately, advancing γδ T cell therapies requires overcoming these hurdles to transition them effectively from the bench to mainstream clinical practice.
Source: Frontiers in Immunology
Authors: Xiaokuan Zhou, Mengqi Zhai, Zhe Zhang, Guojun Zhang
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Funder: China Medical University
OpenAlex ID: W7155550459