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Directed Differentiation of Induced Pluripotent Stem Cells towards T Lymphocytes
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Published on: May 14, 2012

In situ programming of unconventional T cells

Yan-Ruide Li1, Haochen Nan2, Youcheng Yang2

  • 1Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Trends in Biotechnology
|August 14, 2026
PubMed

Unconventional T cells (UTCs), including γδ T cells, mucosal-associated invariant T cells, and natural killer T cells, recognize conserved nonpeptide antigens through semi-invariant T cell receptors in an human leukocyte antigen-independent manner, making them attractive candidates for broadly applicable immunotherapies. However, their clinical translation remains limited by poor spatiotemporal control of activation, functional exhaustion, and insufficient tissue homing in vivo, particularly in solid tumors. Biomaterial-based delivery systems provide a promising strategy to overcome these barriers by enabling localized and sustained delivery of UTC ligands, cytokines, and nucleic acids within diseased tissues. Through precise in situ programming of UTC responses, these platforms may enhance therapeutic efficacy and safety. This review summarizes current biomaterial-based strategies and discusses emerging opportunities for in situ UTC programming in human cancers.

Keywords:
MAIT cellsNKT cellsUTCsbiomaterial-based deliveryin situ immunoengineeringγδ T cells

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