Gamma-delta (γδ) T cells: friend or foe in cancer development?

Abstract

Backgroundγδ T cells are a distinct subgroup of T cells containing T cell receptors (TCRs) γ and TCR δ chains with diverse structural and functional heterogeneity. As a bridge between the innate and adaptive immune systems, γδ 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 γδ T cells in cancer immunotherapy has received a lot of attention over the past decade.Main textDespite the promising potential of γδ T cells, the efficacy of γδ T cell immunotherapy is limited, with an average response ratio of only 21%. In addition, research over the past 2 years has shown that γδ T cells could also promote cancer progression by inhibiting antitumor responses, and enhancing cancer angiogenesis. As a result, γδ 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 γδ T cell immunotherapy, we review recent observations regarding the antitumor and protumor activities of major structural and functional subsets of human γδ 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 γδ T cells used in adoptive immunotherapy, coupled with the fact that γδ T cells can be polarized from antitumor cells to protumor cells appear to be the likely reasons for the mild efficacy seen with γδ T cells.ConclusionThe future holds the promise of depleting the specific protumor γδ T cell subgroup before therapy, choosing multi-immunocyte adoptive therapy, modifying the cytokine balance in the cancer microenvironment, and using a combination of γδ T cells adoptive immunotherapy with immune checkpoint inhibitors.

MAIT cell activation in adolescents is impacted by bile acid concentrations and body weight

“…). In addition to MAIT cells, PLZF is also expressed by invariant NK T (iNK T) cells and Vδ2 γδ T cells . As PLZF mRNA levels were analyzed in whole blood in the present investigation, the signal determined might be influenced by these cell types.…”

ABCA1/ABCB1 Ratio Determines Chemo- and Immune-Sensitivity in Human Osteosarcoma

“…Although the role of γδ T-cells as anti-tumor or pro-tumor population is still controversial, depending on tumor type, γδ T-cells subset, and amount [16,55], Vγ9Vδ2 T-cells are considered the most favorable prognostic factor between the tumor-infiltrating immune populations in 25 different types of solid cancers including osteosarcoma [16]. In our preclinical models, NZ recapitulates what we observed in ex vivo co-culture models: it increased the percentage of necro-apoptotic cells, the ABCA1/ABCB1 ratio and the infiltration of Vγ9Vδ2 T-cells.…”

Preservation of cell-based immunotherapies for clinical trials

“…gd T-cell therapy Another small subset of T cells, gd T cells, has also been investigated for safety and efficiency in immunotherapy due to its broad functionality including production of cytokines and interaction with infected cells or other immune cells [36]. Unlike most T cells, with T-cell receptors (TCRs) composed of an alpha and a beta chain, gd T cells express TCRs composed of a gamma and a delta chain, making the activation of gd T cells Major Histocompatibility Complex-independent.…”