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

Abstract

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.

Coagulation factor V is a marker of tumor-infiltrating immune cells in breast cancer

“…30 The role of B cells and gamma delta T cells in the tumor microenvironment is less understood. 31,32 We also investigated the association between immune cell types and F5 expression in the molecular subtypes. According to the in silico deconvolution of immune cell type signatures there was no consensus between the Scandinavian and the TCGA cohort.…”

Association between αβ and γδ T‑cell subsets and clinicopathological characteristics in patients with breast cancer

“…This cell type is considered to be an unconventional T cell that serves as a link between innate and adaptive immunity. Due to its immune characteristics, it plays a key role in anti-infection and antitumor responses, can produce effective cytotoxicity against malignant tumors, and has the functions of immune surveillance and tumor cell elimination ( 9 ). In the peripheral blood, αβ T cells account for ~95%, while γδ T cells account for only 5% of the total CD3 + cells.…”

ADAM protease inhibition overcomes resistance of breast cancer stem-like cells to γδ T cell immunotherapy

“…In one such study treating breast cancer patients with advanced-stage refractory disease, three of ten patients survived past 12 months and showed durable maintenance of robust γδTc numbers (18). For a recent review of γ δ Tc in breast cancer, please see (19).…”

“…Tc were most differentiated and therefore most cytotoxic by the end of the culture period (days[19][20][21], most experiments including cytotoxicity assays were done on those days. Exceptions were proliferation and inhibitory receptor assays, which were begun earlier in the culturing period.Breast Cancer Cell LinesInflammatory TNBC line SUM149 cells were cultured in Ham's F-12 medium with 5% heatinactivated FBS, 10mM HEPES, 1μg/mL hydrocortisone and 5μg/mL insulin.…”