The emerging role of γδ T cells in cancer immunotherapy

Nussbaumer, Oliver; Koslowski, Michael

doi:10.1016/j.iotech.2019.06.002

Cited by 45 publications

(46 citation statements)

References 110 publications

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“…As innate-like T cells that combine adaptive properties of conventional αβ T cells and innate features of NK cells, γδ T cells are highly attractive candidates for cell-based immunotherapy of infectious and malignant disease [86]. Recently, attempts have been made to equip these already versatile innate-like T cells with additional functions.…”

Section: Discussionmentioning

confidence: 99%

Functional Phenotypes of Human Vγ9Vδ2 T Cells in Lymphoid Stress Surveillance

Nussbaumer

Thurnher

2020

Cells

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Butyrophilin and butyrophilin-like proteins select γδ T cells and direct the migration of γδ T cell subsets to distinct anatomical sites. γδ T cells expressing Vδ2 paired with Vγ9 (Vγ9Vδ2 T cells) are the predominant γδ T cell type in human peripheral blood. Vγ9Vδ2 T cells, which cannot be studied easily in vivo because they do not exist in rodents, are often referred to as innate-like T cells. The genetically recombined γδ T cell receptor (TCR) that responds to isoprenoid-derived pyrophosphates (phosphoantigens) produced by infected and malignant cells in a butyrophilin-dependent manner qualifies them as therapeutically relevant components of the adaptive immune system. On the other hand, cell-surface proteins such as the C-type lectin CD161 mark a functional phenotype of Vγ9Vδ2 T cells that mediates TCR-independent innate-like responses. Moreover, CD56 (neural cell adhesion molecule, NCAM) and the G protein-coupled receptor GPR56 define Vγ9Vδ2 T cells with increased cytolytic potential and, like CD161, may also be expressed by dendritic cells, principally facilitating the generation of an innate-like immunological synapse. In this review, we summarise current knowledge of Vγ9Vδ2 T cell functional phenotypes that are critical to lymphoid stress surveillance.

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Section: Discussionmentioning

confidence: 99%

Functional Phenotypes of Human Vγ9Vδ2 T Cells in Lymphoid Stress Surveillance

Nussbaumer

Thurnher

2020

Cells

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“…Tumor-infiltrating γδ T cells have been considered the most favorable prognostic marker in many types of cancers [55]. While the adoptive transfer of ex vivo-expanded Vδ2 + T cells and even the adoptive transfer of allogeneic γδ T cells shows objective effects, complete remissions still remain anecdotical and the necessary repetitive in vivo activation shows limited responses [56]. The present study, therefore, examined γδ T cells' suppressive behavior as one potential mechanism preventing Vδ2 + T cells from exerting stimulation setting in this order.…”

Section: Discussionmentioning

confidence: 99%

Suppressive activity of Vδ2+ γδ T cells on αβ T cells is licensed by TCR signaling and correlates with signal strength

Schilbach

Krickeberg

Kaißer

et al. 2020

Cancer Immunol Immunother

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Despite recent progress in the understanding of γδ T cells' roles and functions, their interaction with αβ T cells still remains to be elucidated. In this study, we sought to clarify what precisely endows peripheral Vδ2 + T cells with immunosuppressive function on autologous αβ T cells. We found that negatively freshly isolated Vδ2 + T cells do not exhibit suppressive behavior, even after stimulation with IL-12/IL-18/IL-15 or the sheer contact with butyrophilin-3A1-expressing tumor cell lines (U251 or SK-Mel-28). On the other hand, Vδ2 + T cells positively isolated through TCR crosslinking or after prolonged stimulation with isopentenyl pyrophosphate (IPP) mediate strong inhibitory effects on αβ T cell proliferation. Stimulation with IPP in the presence of IL-15 induces the most robust suppressive phenotype of Vδ2 + T cells. This indicates that Vδ2 + T cells' suppressive activity is dependent on a TCR signal and that the degree of suppression correlates with its strength. Vδ2 + T cell immunosuppression does not correlate with their Foxp3 expression but rather with their PD-L1 protein expression, evidenced by the massive reduction of suppressive activity when using a blocking antibody. In conclusion, pharmacologic stimulation of Vδ2 + T cells via the Vδ2 TCR for activation and expansion induces Vδ2 + T cells' potent killer activity while simultaneously licensing them to suppress αβ T cell responses. Taken together, the study is a further step to understand-in more detail-the suppressive activity of Vδ2 + γδ T cells.

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“…Microbial colonization controls MAIT cell development [68]. The clinical relevance of Vγ9 + Vδ2 + T cells has for the most part been studied in the context of cancer immunology, consistent with Vγ9 + Vδ2 + T cells' potent ability to recognize and kill tumour cells [82,83]. However, Vγ9 + Vδ2 + T cells may also play a protective role against malaria and other infectious disease [73,84], due to their ability to recognize microbialderived phosphoantigens [85].…”

Section: Invariant Natural Killer T (Inkt) Cellsmentioning

confidence: 96%

Innate-like T Cells in the Context of Metabolic Disease and Novel Therapeutic Targets

Woude¹,

Krebs²,

Filoche³

et al. 2020

Immunometabolism

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Metabolic diseases continue to rise in global prevalence. Although there is evidence that current methods of treatment are effective, the continued rise in prevalence indicates that alternative, more efficient treatment options are needed. Over the last several years, immune cells have been increasingly studied as important players in the development of a range of diseases, including metabolic diseases such as obesity and obesityinduced type 2 diabetes. This review explores how understanding the intrinsic metabolism of innate-like T cells could provide potential targets for treating metabolic disease, and highlights research areas needed to advance this promising therapeutic approach.

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The emerging role of γδ T cells in cancer immunotherapy

Cited by 45 publications

References 110 publications

Functional Phenotypes of Human Vγ9Vδ2 T Cells in Lymphoid Stress Surveillance

Functional Phenotypes of Human Vγ9Vδ2 T Cells in Lymphoid Stress Surveillance

Suppressive activity of Vδ2+ γδ T cells on αβ T cells is licensed by TCR signaling and correlates with signal strength

Innate-like T Cells in the Context of Metabolic Disease and Novel Therapeutic Targets

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