{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T13:26:15Z","timestamp":1772025975409,"version":"3.50.1"},"reference-count":0,"publisher":"Knowledge E DMCC","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJAAI"],"abstract":"<jats:p>Tumor microenvironment modulators have produced durable effects in cancer treatment. Targeting immune checkpoint receptors, such as PD-L1, has demonstrated efficacy in eliciting antitumor responses. However, resistance to immune checkpoint blockers (ICBs) has constrained the efficacy of these therapies. Previous studies showed a link between the expression of AXL receptor tyrosine kinase and resistance to ICBs. Therefore, designing combination treatments with synergistic mechanisms to overcome ICB-based resistance is needed. In addition to antibody-based therapies, gene silencing with siRNAs has recently been explored to alter the cancer environment to enhance the immune response.\r\nIn this study, we targeted PD-L1 using an siRNA and AXL using a blocker (R428) in OVACAR-3 and CaSki cells, ovarian and cervical cancer cell lines, respectively, in the following groups: Scramble-siRNA, PD-L1-siRNA, Scramble-siRNA in conjunction with R428, PD-L1-siRNA in conjunction with R428, R428 monotherapy and untreated controls. Cell viability was assessed by MTT assay after 48 hours of treatment, and cisplatin sensitization was evaluated in resistant OVACAR-3 cells. Gene expression was analyzed by qRT-PCR, while flow cytometry quantified CD44+PD-L1+ populations, apoptosis (Annexin V\/PI), and cell cycle distribution.\r\nThe results showed a significant decrease in cell proliferation, suppression of EMT-regulating genes, reduction of stemness in cancer cells, increased apoptosis and disruption of the cell cycle in the studied cell lines.\r\nThese findings suggest that simultaneous blockade of PD-L1 and AXL could serve as a novel tumor-suppressive strategy, especially for cancer patients resistant to ICBs.<\/jats:p>","DOI":"10.18502\/ijaai.v25i2.20802","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T10:49:30Z","timestamp":1769510970000},"source":"Crossref","is-referenced-by-count":0,"title":["Dual Blockade of PD-L1 and AXL: A Novel Immunotherapeutic Approach  for Ovarian and Cervical Cancer"],"prefix":"10.18502","author":[{"given":"Hossein","family":"Rahavi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad","family":"Najafi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hossein","family":"Asgarian-Omran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Behrouz","family":"Aflatoonian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohsen","family":"Tehrani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ehsan","family":"Farashahi-Yazd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"7770","published-online":{"date-parts":[[2026,1,27]]},"container-title":["Iranian Journal of Allergy, Asthma and Immunology"],"original-title":[],"link":[{"URL":"https:\/\/publish.kne-publishing.com\/index.php\/IJAAI\/article\/download\/20802\/19451","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/publish.kne-publishing.com\/index.php\/IJAAI\/article\/download\/20802\/19451","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T12:36:36Z","timestamp":1772022996000},"score":1,"resource":{"primary":{"URL":"https:\/\/publish.kne-publishing.com\/index.php\/IJAAI\/article\/view\/20802"},"secondary":[{"URL":"https:\/\/ijaai.tums.ac.ir\/index.php\/ijaai\/article\/view\/4448","label":"UNIVERSITY"}]},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,27]]},"references-count":0,"URL":"https:\/\/doi.org\/10.18502\/ijaai.v25i2.20802","relation":{},"ISSN":["1735-5249","1735-1502"],"issn-type":[{"value":"1735-5249","type":"electronic"},{"value":"1735-1502","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1,27]]}}}