{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T03:12:02Z","timestamp":1778037122169,"version":"3.51.4"},"reference-count":46,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T00:00:00Z","timestamp":1692057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Although the impact of circadian timing on immunotherapy has yet to be integrated into clinical practice, chronoimmunotherapy is an emerging and promising field as circadian oscillations are observed in immune cell numbers as well as the expression of immunotherapy targets, e.g., programmed cell death protein-1 and its ligand programmed death ligand 1. Concurrent retrospective studies suggest that morning infusions may lead to higher effectiveness of immune checkpoint inhibitors in melanoma, non-small cell lung cancer, and kidney cancer. This paper discusses the results of a retrospective study (2016\u20132022) exploring the impact of infusion timing on the outcomes of all 73 patients with stage IV melanoma receiving immunotherapy at a particular medical center. While the median overall survival (OS) was 24.2 months (95% confidence interval [CI] 9.04\u201339.8), for a median follow-up of 15.3 months, our results show that having more than 75% of infusions in the afternoon results in shorter median OS (14.9 vs. 38.1 months; hazard ratio 0.45 [CI 0.23\u20130.86]; p &lt; 0.01) with more expressive impacts on particular subgroups: women, older patients, and patients with a lower tumor burden at the outset of immunotherapy. Our findings highlight the potential benefits of follow-up validation in prospective and translational randomized studies.<\/jats:p>","DOI":"10.3390\/cells12162068","type":"journal-article","created":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T11:09:44Z","timestamp":1692097784000},"page":"2068","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Immunotherapy around the Clock: Impact of Infusion Timing on Stage IV Melanoma Outcomes"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3431-5217","authenticated-orcid":false,"given":"Lisa","family":"Gon\u00e7alves","sequence":"first","affiliation":[{"name":"Department of Oncology, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-035 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8586-6078","authenticated-orcid":false,"given":"Duarte","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Department of Economics, University College London, London WC1H 0AX, UK"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7034-4812","authenticated-orcid":false,"given":"Teresa","family":"Esteban-Casanelles","sequence":"additional","affiliation":[{"name":"Department of Political Economy, King\u2019s College London, London WC2B 4BG, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4854-1642","authenticated-orcid":false,"given":"Tiago","family":"Barroso","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-035 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8377-0179","authenticated-orcid":false,"given":"In\u00eas","family":"Soares de Pinho","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-035 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8976-3199","authenticated-orcid":false,"given":"Raquel","family":"Lopes-Br\u00e1s","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-035 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6858-7341","authenticated-orcid":false,"given":"Miguel","family":"Esperan\u00e7a-Martins","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-035 Lisboa, Portugal"},{"name":"Instituto de Medicina Molecular-Jo\u00e3o Lobo Antunes, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal"}]},{"given":"Vanessa","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-035 Lisboa, Portugal"}]},{"given":"Sofia","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-035 Lisboa, Portugal"}]},{"given":"Rita","family":"Teixeira de Sousa","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-035 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8771-0838","authenticated-orcid":false,"given":"Andr\u00e9","family":"Mansinho","sequence":"additional","affiliation":[{"name":"START Lisbon, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-035 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4782-7318","authenticated-orcid":false,"given":"Lu\u00eds","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-035 Lisboa, Portugal"},{"name":"Instituto de Medicina Molecular-Jo\u00e3o Lobo Antunes, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2020033","DOI":"10.5826\/dpc.1003a33","article-title":"Melanoma Epidemiology and Early Detection in Europe: Diversity and Disparities","volume":"10","author":"Forsea","year":"2020","journal-title":"Dermatol. 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