Background: gamma delta T cells are a distinct subgroup of T cells containing T cell receptors (TCRs)gamma and TCR delta chains with diverse structural and functional heterogeneity. As a bridge between the innate and adaptive immune systems,gamma delta T cells participate in various immune responses during cancer progression. Because of their direct/indirect antitumor cytotoxicity and strong cytokine production ability, the use of gamma delta T cells in cancer immunotherapy has received a lot of attention over the past decade.
Main text: Despite the promising potential of gamma delta T cells, the efficacy of gamma delta T cell immunotherapy is limited, with an average response ratio of only 21%. In addition, research over the past 2 years has shown that gamma delta T cells could also promote cancer progression by inhibiting antitumor responses, and enhancing cancer angiogenesis. As a result,gamma delta T cells have a dual effect and can therefore be considered as being both "friends" and "foes" of cancer. In order to solve the sub-optimal efficiency problem of gamma delta T cell immunotherapy, we review recent observations regarding the antitumor and protumor activities of major structural and functional subsets of human gamma delta T cells, describing how these subsets are activated and polarized, and how these events relate to subsequent effects in cancer immunity. A mixture of both antitumor or protumor gamma delta T cells used in adoptive immunotherapy, coupled with the fact that gamma delta T cells can be polarized from antitumor cells to protumor cells appear to be the likely reasons for the mild efficacy seen with gamma delta T cells.
Conclusion: The future holds the promise of depleting the specific protumor gamma delta T cell subgroup before therapy, choosing multi-immunocyte adoptive therapy, modifying the cytokine balance in the cancer microenvironment, and using a combination of gamma delta T cells adoptive immunotherapy with immune checkpoint inhibitors.
[1]Jilin Univ, Hosp 1, Canc Ctr, Changchun 130021, Jilin, Peoples R China.
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