János Bolyai Research Scholarship of the Hungarian Academy of Sciences(TKP2021-NVA-15)
The tumor microenvironment (TME) has gained considerable scientific attention by playing
a role in immunosuppression and tumorigenesis. Besides tumor cells, TME is composed
of various other cell types, including cancer-associated fibroblasts (CAFs or MAFs
when referring to melanoma-derived CAFs) and tumor-infiltrating lymphocytes (TILs),
a subpopulation of which is labeled as γδ T cells. Since the current anti-cancer therapies
using γδ T cells in various cancers have exhibited mixed treatment responses, to better
understand the γδ T cell biology in melanoma, our research group aimed to investigate
whether activated γδ T cells are capable of killing MAFs. To answer this question,
we set up an in vitro platform using freshly isolated Vδ2-type γδ T cells and cultured
MAFs that were biobanked from our melanoma patients. This study proved that the addition
of zoledronic acid (1–2.5 µM) to the γδ T cells was necessary to drive MAFs into apoptosis.
The MAF cytotoxicity of γδ T cells was further enhanced by using the stimulatory clone
20.1 of anti-BTN3A1 antibody but was reduced when anti-TCR γδ or anti-BTN2A1 antibodies
were used. Since the administration of zoledronic acid is safe and tolerable in humans,
our results provide further data for future clinical studies on the treatment of melanoma.
