γδ T cell exhaustion: Opportunities for intervention

T lymphocytes are the key protective contributors in chronic infection and tumor, but experience exhaustion by persistent antigen stimulation. As an unconventional lineage of T cells, gamma delta T cells can rapidly response to varied infectious and tumor challenges in a non-MHC-restricted manner and play key roles in immune surveillance via pleiotropic effector functions, showing promising as candidates for cellular tumor immunotherapy. Activated gamma delta T cells can also acquire exhaustion signature with elevated expression of immune checkpoints, such as PD-1, decreased cytokine production, and functional impairment. However, the exhaustion features of gamma delta T cells are distinct from conventional alpha beta T cells. Here, we review the researches regarding the characteristics, heterogeneity, and mechanisms of gamma delta T cell exhaustion. These studies provide insights into the combined strategies to overcome the exhaustion of gamma delta T cells and enhance antitumor immunity. Summary sentence: Review of the characteristics, heterogeneity, and mechanisms of gamma delta T cell exhaustion provides insights into the combined strategies to enhance gamma delta T cellbased antitumor immunotherapy.

Automated summary

Reviewing the characteristics, heterogeneity, and mechanisms of gamma delta T cell exhaustion provides insights into the combined strategies to enhance gamma delta T cell-based antitumor immunotherapy.