Dual Face of Vγ9Vδ2-T Cells in Tumor Immunology: Anti- versus Pro-Tumoral Activities

Xiang, Zheng; Tu, Wenwei

doi:10.3389/fimmu.2017.01041

Cited by 51 publications

(42 citation statements)

References 159 publications

(205 reference statements)

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“…21 γδ T cells utilize a variety of surface receptors and cytokines, such as NKG2D, TRAIL, FASL, TNF-α, IFN-γ, Granzyme B, and perforin, to initiate cytotoxicity against cancer cells. [11][12][13]22,23 In addition, given that different subtypes of γδ T cells possess diverse functional signatures, investigations on total γδ T cells in the context of the tumor microenvironment or immunotherapy tend to produce controversial results; for example, there are inconsistent views 24 on the intratumoral γδ T-cell signature as the most favorable prognostic biomarker 25 of cancers and discussions on the pro-and antitumor activities of γδ T cells. 22,26 Nevertheless, Vγ9Vδ2 T cells have promising clinical value and advantages for tumor immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer

et al. 2020

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Vγ9Vδ2 T cells are promising candidates for cellular tumor immunotherapy. Due to their HLA-independent mode of action, allogeneic Vγ9Vδ2 T cells can be considered for clinical application. To apply allogeneic Vγ9Vδ2 T cells in adoptive immunotherapy, the methodology used to obtain adequate cell numbers with optimal effector function in vitro needs to be optimized, and clinical safety and efficacy also need to be proven. Therefore, we developed a novel formula to improve the expansion of peripheral γδ T cells from healthy donors. Then, we used a humanized mouse model to validate the therapeutic efficacy of expanded γδ T cells in vivo; furthermore, the expanded γδ T cells were adoptively transferred into late-stage liver and lung cancer patients. We found that the expanded cells possessed significantly improved immune effector functions, including proliferation, differentiation, and cancer cell killing, both in vitro and in the humanized mouse model. Furthermore, a phase I clinical trial in 132 late-stage cancer patients with a total of 414 cell infusions unequivocally validated the clinical safety of allogeneic Vγ9Vδ2 T cells. Among these 132 patients, 8 liver cancer patients and 10 lung cancer patients who received ≥5 cell infusions showed greatly prolonged survival, which preliminarily verified the efficacy of allogeneic Vγ9Vδ2 T-cell therapy. Our clinical studies underscore the safety and efficacy of allogeneic Vγ9Vδ2 T-cell immunotherapy, which will inspire further clinical investigations and eventually benefit cancer patients.

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Section: Introductionmentioning

confidence: 99%

Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer

et al. 2020

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“…Vδ2 T cells activated by non-peptide phosphoantigens in vitro have been proven to inhibit tumor growth both in vitro and in vivo (40,41). Currently, the results of phase I clinical trials on advanced lung cancer, renal cancer and melanoma have revealed that adoptive Vδ2 T cell transfer therapies have shown certain antitumor effects (42). However, other studies have reported that Vδ2 T cells can also promote tumor progression (43).…”

Section: Discussionmentioning

confidence: 99%

High Abundance of Intratumoral γδ T Cells Favors a Better Prognosis in Head and Neck Squamous Cell Carcinoma: A Bioinformatic Analysis

Wei

Guo

et al. 2020

Front. Immunol.

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γδ T cells are a small subset of unconventional T cells that are enriched in the mucosal areas, and are responsible for pathogen clearance and maintaining integrity. However, the role of γδ T cells in head and neck squamous cell carcinoma (HNSCC) is largely unknown. Here, by using RNA-seq data from The Cancer Genome Atlas (TCGA), we discovered that HNSCC patients with higher levels of γδ T cells were positively associated with lower clinical stages and better overall survival, and high abundance of γδ T cells was positively correlated with CD8+/CD4+ T cell infiltration. Gene ontology and pathway analyses showed that genes associated with T cell activation, proliferation, effector functions, cytotoxicity, and chemokine production were enriched in the group with a higher γδ T cell abundance. Furthermore, we found that the abundance of γδ T cells was positively associated with the expression of the butyrophilin (BTN) family proteins BTN3A1/BTN3A2/BTN3A3 and BTN2A1, but only MICB, one of the ligands of NKG2D, was involved in the activation of γδ T cells, indicating that the BTN family proteins might be involved in the activation and proliferation of γδ T cells in the tumor microenvironment of HNSCC. Our results indicated that γδ T cells, along with their ligands, are promising targets in HNSCC with great prognostic values and treatment potentials.

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“…However, more recent evidence in colorectal, ovarian and breast cancer has suggested that γδT lymphocytes may also have a pro-tumourigenic role (8)(9)(10). Several reviews over the last few years have described the role of γδT lymphocytes in cancer in general (11)(12)(13)(14)(15), but this review will summarise the evidence to date regarding γδT lymphocytes in breast cancer.…”

Section: The Role Of Gamma Delta T Lymphocytes In Breast Cancer: a Rementioning

confidence: 99%

The role of gamma delta T lymphocytes in breast cancer: a review

Morrow

Roseweir

Edwards

2019

Translational Research

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Gammadelta T (γδT) lymphocytes have provoked interest in oncology, particularly as regards their potential use in immunotherapy, because of their unique ability to recognise antigens without a requirement for major histocompatibility complex antigen presentation, and to quickly activate an anti-tumour response. However, work in some cancers has suggested that they also have pro-tumourigenic activity. Their role in breast cancer is unclear. This review outlines the evidence to date in in vitro studies, in vivo mouse models and in human studies regarding the role of γδT lymphocytes in breast cancer. We describe the seemingly opposing roles of the predominantly circulating Vγ9Vδ2 subtype, which can suppress tumour growth through direct cytotoxicity, induction of apoptosis and inhibition of angiogenesis, and the predominantly tumour-infiltrating γδ1 subtype which can promote tumour growth and spread through immunosuppressant effects. We summarise the evidence in breast cancer for the mechanisms of action of γδT lymphocytes and describe how factors in the tumour microenvironment may affect their function, polarising them towards a pro-tumourigenic, immune-suppressing role. We also describe the experience to date of γδT lymphocytes in immunotherapy for breast cancer and suggest the direction of work going forward, particularly as regards different breast cancer subtypes.

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Dual Face of Vγ9Vδ2-T Cells in Tumor Immunology: Anti- versus Pro-Tumoral Activities

Cited by 51 publications

References 159 publications

Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer

Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer

High Abundance of Intratumoral γδ T Cells Favors a Better Prognosis in Head and Neck Squamous Cell Carcinoma: A Bioinformatic Analysis

The role of gamma delta T lymphocytes in breast cancer: a review

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