{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T19:42:45Z","timestamp":1769629365027,"version":"3.49.0"},"reference-count":55,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T00:00:00Z","timestamp":1692230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hungarian National Research, Development, and Innovation Office","award":["NN 114460"],"award-info":[{"award-number":["NN 114460"]}]},{"name":"Hungarian National Research, Development, and Innovation Office","award":["TKP2021-NVA-15"],"award-info":[{"award-number":["TKP2021-NVA-15"]}]},{"name":"Semmelweis University Dean\u2019s Award","award":["NN 114460"],"award-info":[{"award-number":["NN 114460"]}]},{"name":"Semmelweis University Dean\u2019s Award","award":["TKP2021-NVA-15"],"award-info":[{"award-number":["TKP2021-NVA-15"]}]},{"name":"Semmelweis University","award":["NN 114460"],"award-info":[{"award-number":["NN 114460"]}]},{"name":"Semmelweis University","award":["TKP2021-NVA-15"],"award-info":[{"award-number":["TKP2021-NVA-15"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u03b3\u03b4 T cells. Since the current anti-cancer therapies using \u03b3\u03b4 T cells in various cancers have exhibited mixed treatment responses, to better understand the \u03b3\u03b4 T cell biology in melanoma, our research group aimed to investigate whether activated \u03b3\u03b4 T cells are capable of killing MAFs. To answer this question, we set up an in vitro platform using freshly isolated V\u03b42-type \u03b3\u03b4 T cells and cultured MAFs that were biobanked from our melanoma patients. This study proved that the addition of zoledronic acid (1\u20132.5 \u00b5M) to the \u03b3\u03b4 T cells was necessary to drive MAFs into apoptosis. The MAF cytotoxicity of \u03b3\u03b4 T cells was further enhanced by using the stimulatory clone 20.1 of anti-BTN3A1 antibody but was reduced when anti-TCR \u03b3\u03b4 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.<\/jats:p>","DOI":"10.3390\/ijms241612893","type":"journal-article","created":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T10:15:48Z","timestamp":1692267348000},"page":"12893","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Targeting Melanoma-Associated Fibroblasts (MAFs) with Activated \u03b3\u03b4 (V\u03b42) T Cells: An In Vitro Cytotoxicity Model"],"prefix":"10.3390","volume":"24","author":[{"given":"Anna","family":"Hajdara","sequence":"first","affiliation":[{"name":"Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary"},{"name":"Roska Tam\u00e1s Doctoral School of Sciences and Technology, Faculty of Information Technology and Bionics, P\u00e1zm\u00e1ny P\u00e9ter Catholic University, 1083 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"U\u011fur","family":"\u00c7ak\u0131r","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"\u00c9rsek","sequence":"additional","affiliation":[{"name":"Department of Genetics, Cell and Immunobiology, Semmelweis University, 1089 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e1lma","family":"Sill\u00f3","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bal\u00e1zs","family":"Sz\u00e9ky","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary"},{"name":"Roska Tam\u00e1s Doctoral School of Sciences and Technology, Faculty of Information Technology and Bionics, P\u00e1zm\u00e1ny P\u00e9ter Catholic University, 1083 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8895-3062","authenticated-orcid":false,"given":"G\u00e1bor","family":"Barna","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaaban","family":"Faqi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary"},{"name":"K\u00e1roly R\u00e1cz Doctoral School of Clinical Medicine, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikl\u00f3s","family":"Gy\u00f6ngy","sequence":"additional","affiliation":[{"name":"Faculty of Information Technology and Bionics, P\u00e1zm\u00e1ny P\u00e9ter Catholic University, 1083 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarolta","family":"K\u00e1rp\u00e1ti","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kriszti\u00e1n","family":"N\u00e9meth","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bal\u00e1zs","family":"Mayer","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.semcdb.2009.10.010","article-title":"Cancer associated fibroblasts in cancer pathogenesis","volume":"21","author":"Franco","year":"2010","journal-title":"Semin. 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