{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:53:37Z","timestamp":1778644417911,"version":"3.51.4"},"reference-count":34,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of General Medical Sciences at the NIH","award":["R16 GM145561"],"award-info":[{"award-number":["R16 GM145561"]}]},{"name":"National Institute of General Medical Sciences at the NIH","award":["R16 GM153947"],"award-info":[{"award-number":["R16 GM153947"]}]},{"name":"NIH\/NIGMS","award":["R16 GM145561"],"award-info":[{"award-number":["R16 GM145561"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Programmed death ligand 1 (PD-L1) is often overexpressed in triple-negative breast cancer (TNBC), where it helps the tumor evade the immune system and promotes tumor growth. Interleukin-24 (IL-24) is recognized for its anti-tumor activity, although its role in immune regulation remains unclear. In this study, we examined the role of IL-24 in regulating PD-L1 and its anti-cancer activity in TNBC cells. Methods: The study used TNBC cell lines treated with IL-24, delivered via a non-replicating adenovirus vector expressing the IL-24 gene. Assays included MTT for cell viability, Annexin V for apoptosis, Western blot for protein analysis, and qRT-PCR for mRNA analysis. Results: We found that the highly aggressive MDA-MB-231 cells had significantly higher PD-L1 levels. We discovered that treatment with IL-24 reduced cell growth, induced apoptosis, and significantly decreased PD-L1 protein levels in MDA-MB-231 cells. Mechanistically, we identified PKR, also known as eukaryotic translation initiation factor 2 alpha kinase 2, as a key mediator of IL-24\u2013induced PD-L1 suppression. Additionally, doxorubicin, a primary chemotherapy drug used to treat triple-negative breast cancer, decreases PD-L1 expression and increases the sensitivity when combined with IL-24. Conclusions: In this study, we show that IL-24 decreases PD-L1 expression in MDA-MB-231 cells through PKR activation, enhances the anti-tumor effects of Doxorubicin, and may enable lower doses that reduce toxicity and further decrease PD-L1 levels. These findings suggest that IL-24 could serve as a valuable target for therapeutic intervention and suggest that it can improve doxorubicin\u2019s effectiveness against aggressive breast cancer.<\/jats:p>","DOI":"10.3390\/genes17030339","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T11:50:36Z","timestamp":1773921036000},"page":"339","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibitory Effect of Interleukin-24 on Programmed Death Ligand 1 Expression via a Eukaryotic Translation Initiation Factor 2 Alpha Kinase 2-Dependent Pathway in Human Triple-Negative Breast Cancer"],"prefix":"10.3390","volume":"17","author":[{"given":"Simira","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5156-9051","authenticated-orcid":false,"given":"Anastassiya","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA"},{"name":"Ph.D. Program in Biology, The Graduate Center, City University of New York, 365 Fifth Avenue, New York, NY 10016, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alphons","family":"Sony","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryam","family":"Aslam","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA"},{"name":"Ph.D. Program in Biology, The Graduate Center, City University of New York, 365 Fifth Avenue, New York, NY 10016, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elouise","family":"Torruella","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5438-8157","authenticated-orcid":false,"given":"Columba","family":"de la Parra","sequence":"additional","affiliation":[{"name":"Ph.D. Program in Biology, The Graduate Center, City University of New York, 365 Fifth Avenue, New York, NY 10016, USA"},{"name":"Department of Chemistry, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2710-3491","authenticated-orcid":false,"given":"Moira","family":"Sauane","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA"},{"name":"Ph.D. Program in Biology, The Graduate Center, City University of New York, 365 Fifth Avenue, New York, NY 10016, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1097\/BS9.0000000000000149","article-title":"PD-L1: Expression regulation","volume":"5","author":"Zhou","year":"2023","journal-title":"Blood Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S1359-6101(02)00074-6","article-title":"MDA-7\/IL-24: Novel cancer growth suppressing and apoptosis inducing cytokine","volume":"14","author":"Sauane","year":"2003","journal-title":"Cytokine Growth Factor. 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