{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:26Z","timestamp":1787028566282,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research, Development, and Innovation Office","award":["OTKA K147482"],"award-info":[{"award-number":["OTKA K147482"]}]},{"name":"HUN-REN Hungarian Research Network","award":["OTKA K147482"],"award-info":[{"award-number":["OTKA K147482"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The resistance of breast cancer cells to therapeutic antibodies such as anti-HER2 trastuzumab can be overcome by engaging natural killer (NK) cells for killing antibody-binding tumor cells via antibody-dependent cellular cytotoxicity (ADCC). Here, we investigated how autophagy modulation affects trastuzumab-mediated ADCC in HER2-positive JIMT1 breast cancer cells and NK cells. Autophagy inducers (rapamycin and resveratrol) had no significant impact, but the inhibitor bafilomycin nearly abolished ADCC. Protection occurred when either cancer or NK cells were pretreated, indicating dual effects. Bafilomycin reduced phosphatidylserine externalization, the loss of plasma membrane integrity, caspase-3\/7 activity, and DNA fragmentation. It downregulated pro-apoptotic BAK1 and BAX without altering BCL-2. Additionally, bafilomycin decreased HER2 surface expression, impairing trastuzumab binding, and modulated immune regulators (STAT1, CD95, and PD-L1) in NK and\/or in the cancer cells. Bafilomycin disrupted HER2 trafficking and induced HER2 internalization, leading to its accumulation in cytoplasmic vesicles. These findings show that autophagy inhibition by bafilomycin confers ADCC resistance by altering apoptosis, immune signaling, and HER2 dynamics. The study underscores autophagy\u2019s role in antibody-based cancer therapy efficacy.<\/jats:p>","DOI":"10.3390\/ijms26136273","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T06:56:54Z","timestamp":1751353014000},"page":"6273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Autophagy Inhibitor Bafilomycin Inhibits Antibody-Dependent Natural Killer Cell-Mediated Killing of Breast Carcinoma Cells"],"prefix":"10.3390","volume":"26","author":[{"given":"\u00c1kos M.","family":"Bede","sequence":"first","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem T\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"National Academy of Scientist Education, Egyetem T\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csongor","family":"V\u00e1r\u00f3czy","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem T\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"National Academy of Scientist Education, Egyetem T\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7600-9672","authenticated-orcid":false,"given":"Zsuzsanna","family":"Polg\u00e1r","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem T\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"Division of Dental Biochemistry, Department of Basic Medical Sciences, Faculty of Dentistry, University of Debrecen, Egyetem T\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerg\u0151","family":"Fazekas","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem T\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"HUN-REN-DE (Hungarian Reasearch Network\u2014University of Debrecen) Cell Biology and Signaling Research Group, Egyetem T\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8575-691X","authenticated-orcid":false,"given":"Csaba","family":"Heged\u0171s","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem T\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"HUN-REN-DE (Hungarian Reasearch Network\u2014University of Debrecen) Cell Biology and Signaling Research Group, Egyetem T\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2035-8408","authenticated-orcid":false,"given":"Endre","family":"K\u00f3kai","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem T\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"Division of Dental Biochemistry, Department of Basic Medical Sciences, Faculty of Dentistry, University of Debrecen, Egyetem T\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem T\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"HUN-REN-DE (Hungarian Reasearch Network\u2014University of Debrecen) Cell Biology and Signaling Research Group, Egyetem T\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7099-6718","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"Vir\u00e1g","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem T\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"HUN-REN-DE (Hungarian Reasearch Network\u2014University of Debrecen) Cell Biology and Signaling Research Group, Egyetem T\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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