Gamma delta T-cell-based immune checkpoint therapy: attractive candidate for antitumor treatment

摘要

As a nontraditional T-cell subgroup, gamma delta T cells have gained popularity in the field of immunotherapy in recent years. They have extraordinary antitumor potential and prospects for clinical application. Immune checkpoint inhibitors (ICIs), which are efficacious in tumor patients, have become pioneer drugs in the field of tumor immunotherapy since they were incorporated into clinical practice. In addition, gamma delta T cells that have infiltrated into tumor tissues are found to be in a state of exhaustion or anergy, and there is upregulation of many immune checkpoints (ICs) on their surface, suggesting that gamma delta T cells have a similar ability to respond to ICIs as traditional effector T cells. Studies have shown that targeting ICs can reverse the dysfunctional state of gamma delta T cells in the tumor microenvironment (TME) and exert antitumor effects by improving gamma delta T-cell proliferation and activation and enhancing cytotoxicity. Clarification of the functional state of gamma delta T cells in the TME and the mechanisms underlying their interaction with ICs will solidify ICIs combined with gamma delta T cells as a good treatment option.

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