{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:07:20Z","timestamp":1790705240290,"version":"4.1.0"},"reference-count":157,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T00:00:00Z","timestamp":1657497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Monoclonal antibodies targeting the PD-1\/PD-L1 immune checkpoint have considerably improved the treatment of some cancers, but novel drugs, new combinations, and treatment modalities are needed to reinvigorate immunosurveillance in immune-refractory tumors. An option to elicit antitumor immunity against cancer consists of using approved and marketed drugs known for their capacity to modulate the expression and functioning of the PD-1\/PD-L1 checkpoint. Here, we have reviewed several types of drugs known to alter the checkpoint, either directly via the blockade of PD-L1 or indirectly via an action on upstream effectors (such as STAT3) to suppress PD-L1 transcription or to induce its proteasomal degradation. Specifically, the repositioning of the approved drugs liothyronine, azelnidipine (and related dihydropyridine calcium channel blockers), niclosamide, albendazole\/flubendazole, and a few other modulators of the PD-1\/PD-L1 checkpoint (repaglinide, pimozide, fenofibrate, lonazolac, propranolol) is presented. Their capacity to bind to PD-L1 or to repress its expression and function offer novel perspectives for combination with PD-1 targeted biotherapeutics. These known and affordable drugs could be useful to improve the therapy of cancer.<\/jats:p>","DOI":"10.3390\/cancers14143368","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T21:57:53Z","timestamp":1657576673000},"page":"3368","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Drug Repurposing to Enhance Antitumor Response to PD-1\/PD-L1 Immune Checkpoint Inhibitors"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0998-4160","authenticated-orcid":false,"given":"Xavier","family":"Thuru","sequence":"first","affiliation":[{"name":"University of Lille, CNRS, Inserm, CHU Lille, UMR9020-UMR1277\u2014Canther\u2014Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1882-8469","authenticated-orcid":false,"given":"Romain","family":"Magnez","sequence":"additional","affiliation":[{"name":"University of Lille, CNRS, Inserm, CHU Lille, UMR9020-UMR1277\u2014Canther\u2014Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassiba","family":"El-Bouazzati","sequence":"additional","affiliation":[{"name":"University of Lille, CNRS, Inserm, CHU Lille, UMR9020-UMR1277\u2014Canther\u2014Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9rard","family":"Vergoten","sequence":"additional","affiliation":[{"name":"Institut de Chimie Pharmaceutique Albert Lespagnol (ICPAL), Facult\u00e9 de Pharmacie, University of Lille, Inserm, INFINITE\u2014U1286, 3 Rue du Professeur Laguesse, BP-83, F-59006 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6563-2709","authenticated-orcid":false,"given":"Bruno","family":"Quesnel","sequence":"additional","affiliation":[{"name":"University of Lille, CNRS, Inserm, CHU Lille, UMR9020-UMR1277\u2014Canther\u2014Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2973-9357","authenticated-orcid":false,"given":"Christian","family":"Bailly","sequence":"additional","affiliation":[{"name":"Oncowitan, Scientific Consulting Office, F-59290 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12943-021-01489-2","article-title":"Combination strategies with PD-1\/PD-L1 blockade: Current advances and future directions","volume":"21","author":"Yi","year":"2022","journal-title":"Mol. 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