| Summary: | The frequent downregulation or complete loss of major histocompatibility complex (MHC) expression by tumour cells often compromises patients’ response to standard cancer treatments or αβ T-cell-based therapies. Thus, NK cell and ɣδ T-cell-based cancer immunotherapies emerged as complementary treatments. Both immunotherapies have been successfully used to target haematological malignancies but their effectiveness in patients with solid tumours has limited their therapeutic application. Most NK cell and ɣδ T-cell-based immunotherapies use cells isolated and expanded from peripheral blood mononuclear cells, which may result in a cellular product with low homing capacity and/or anti-tumour reactivity. We aimed therefore to explore the feasibility of isolating and expanding tumour-reactive NK cells or ɣδ T-cells directly from the tumour tissue of patients with cancer. Different expansion protocols using cytokine combinations of IL-2, IL-15, IL-7 or IL-1β along with molecularly defined targets for ɣδ T-cells were tested for their capacity to preferentially isolate and expand ɣδ T-cells from patients’ tumour, while IL-2, IL-15 and stimulation with the K-562 cell line was used for NK cell isolation and expansion. The protocols’ efficiency was assessed by evaluating the total cell number, cell viability and NK cells or ɣδ T-cells’ frequency. Cells’ functional capacity was determined by their ability to produce IFN-ɣ in response to autologous tumour cells and/or allogeneic cancer cell lines. We demonstrate that NK cells and ɣδ T-cells can be directly isolated from patients’ tumour tissue and are able to recognize autologous tumour cells, producing IFN-ɣ. Tumour-infiltrating ɣδ T-cells revealed inclusive to use their T-cell receptor to target autologous tumour cells in vitro. In summary, our data provide the first evidence that tumour-infiltrating NK cells and γδ T-cells can be expanded from cancer lesions and may be used in cancer immunotherapy for patients with solid tumours.
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