γδ T cells in cancer immunotherapy

Abstract

γδ T cells are one of the three immune cell types that express antigen receptors. They contribute to lymphoid antitumor surveillance and bridge the gap between innate and adaptive immunity. γδ T cells have the capacity of secreting abundant cytokines and exerting potent cytotoxicity against a wide range of cancer cells. γδ T cells exhibit important roles in immune-surveillance and immune defense against tumors and have become attractive effector cells for cancer immunotherapy. γδ T cells mediate anti-tumor therapy mainly by secreting pro-apoptotic molecules and inflammatory cytokines, or through a TCR-dependent pathway. Recently, γδ T cells are making their way into clinical trials. Some clinical trials demonstrated that γδ T cell-based immunotherapy is well tolerated and efficient. Despite the advantages that could be exploited, there are obstacles have to be addressed for the development of γδ T cell immunotherapies. Future direction for immunotherapy using γδ T cells should focus on overcoming the side effects of γδ T cells and exploring better antigens that help stimulating γδ T cell expansion in vitro.

WITHDRAWN: Overexpression of miR-382 sensitizes hepatocellular carcinoma cells to γδ T cells through inhibiting the expression of c-FLIP

“…Subsequently, the mitochondrial permeability transition pore is open and then cytochrome c and Smac/DIABLO which are apoptotic inducers derived from mitochondria will be released into cytoplasm. Finally, caspase-9 and caspase-3 are cleaved and apoptosis occurs in cancer cells [19,21,31,32]. Consistent with these reports, our results emphasized the importance of TRAIL and FasL in γδ T cells-mediated cell lysis in HCC.…”

“…TRAIL and FasL which are secreted by γδ T cells have been reported to participate in the specific killing of tumor cells [18,19]. In accordance with this, we observed significant reduction of cell lysis in γδ T cellstreated HepG2 and PLC cells after they were incubated with TRAIL and FasL neutralizing antibodies ( Figure 3A).…”

γδ T cells in cancer: a small population of lymphocytes with big implications

“…114 This provides a unique advantage for cd T cells over conventional ab T cells. 119,120 These early trials should be interpreted with caution as they were designed for assessing safety of cd T-cell products and not their efficacy. However, Vd1 + T cells have been poorly characterised in solid tumors.…”

“…119 Ex vivo expansion of cd T cells using zoledronate and IL-2 has also been trialled in a number of studies, improving disease progression but failing to achieve improved overall survival in a number of solid tumor types (renal cell carcinoma, lung cancer, hepatocellular carcinoma). 119,120 These early trials should be interpreted with caution as they were designed for assessing safety of cd T-cell products and not their efficacy. As of March 2019, there are currently 13 active clinical trials (clinicaltrials.gov) involving the use of cd T cells to treat a broad range of cancers including leukaemia and breast, pancreatic, ovarian, liver, kidney, lung and brain cancers.…”

Armed oncolytic viruses: A kick-start for anti-tumor immunity

“…The anti-tumor response starts with the release of tumor associated antigens (TAA) from dying cancer cells and accompanying signal molecules, which attract and activate cells of the innate immune system [2,3]. Whereas NK and γd-T cells can recognize and kill tumor cells directly, antigen presenting cells (APCs), such as DCs and macrophages, take up TAAs to activate the adaptive immune system [4,5]. The maturation of APCs by the accompanying danger signal molecules determines the skewing to a preferred T helper cell (Th) 1 response.…”