{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:03:29Z","timestamp":1789657409035,"version":"4.0.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive, routinely available marker of systemic inflammation that has been proposed as a prognostic biomarker in cancer immunotherapy. However, most evidence derives from single baseline measurements in selected populations, and the prognostic value of\n                      <jats:italic>serial, on-treatment<\/jats:italic>\n                      NLR dynamics, particularly in real-world Latin American cohorts, remains poorly defined. We evaluated whether baseline and time-varying NLR predict overall survival (OS) in patients treated with immune checkpoint inhibitors (ICI), and whether any association is independent of performance status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed 68 patients with advanced solid tumors (lung, urological, melanoma, and others) treated with ICI at two Uruguayan institutions: Hospital de Cl\u00ednicas, Universidad de la Rep\u00fablica, and Instituto Nacional del C\u00e1ncer (INCA), both in Montevideo, Uruguay. NLR and platelet-to-lymphocyte ratio (PLR) were measured at baseline and at each treatment cycle (up to 12 cycles). OS and progression-free survival were analyzed using Kaplan\u2013Meier estimates and Cox proportional-hazards models, including a time-varying covariate model using serial NLR. Six-month RECIST response and immune-related adverse events were assessed as secondary outcomes. Robustness was evaluated with bootstrap confidence intervals, permutation testing, and correction for multiple comparisons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Over a median follow-up of 16.8 months, 39 deaths occurred (survival population n=66). Elevated baseline NLR was associated with shorter OS (HR 1.18 per unit, 95% CI 1.04\u20131.34, p=0.011). In a time-varying analysis using serial measurements, higher on-treatment NLR remained independently associated with OS after adjustment for ECOG performance status (HR 1.09, 95% CI 1.00\u20131.19, p=0.040; ECOG p=0.021). Patients in the highest NLR quartile (&amp;gt;4.9) had markedly shorter median OS than the remainder of the cohort (7.3 vs ~25 months). Neither baseline nor dynamic NLR\/PLR predicted six-month RECIST response. Combination anti-PD-1\/anti-CTLA-4 therapy was associated with higher odds of immune-related toxicity (OR 5.03, p=0.023).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this real-world Latin American ICI cohort, dynamic on-treatment NLR was independently associated with overall survival, supporting serial monitoring of this inexpensive marker over single baseline assessment. NLR did not predict tumor response, underscoring that its prognostic value reflects systemic host condition rather than direct antitumor activity. These findings, though exploratory, support NLR trajectory as a low-cost prognostic adjunct warranting prospective validation. Since complete blood counts are already obtained at every treatment cycle for routine hematologic surveillance, this information could be captured at no additional cost to clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1930031","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:11:01Z","timestamp":1789654261000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic neutrophil-to-lymphocyte ratio as an independent prognostic marker of overall survival in patients receiving immune checkpoint inhibitors: a Latin American cohort study"],"prefix":"10.3389","volume":"16","author":[{"given":"Parag","family":"Chatterjee","sequence":"first","affiliation":[{"name":"Department of Biological Engineering, Universidad de la Rep\u00fablica","place":["Paysand\u00fa, Uruguay"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n","family":"Insagaray","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Hospital de Cl\u00ednicas","place":["Montevideo, Uruguay"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1s","family":"Ferraz","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Universidad de la Rep\u00fablica","place":["Paysand\u00fa, Uruguay"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Statistics, Universidad de la Rep\u00fablica","place":["Salto, Uruguay"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianina","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Hospital de Cl\u00ednicas","place":["Montevideo, Uruguay"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Pombo","sequence":"additional","affiliation":[{"name":"Instituto Nacional del C\u00e1ncer (National Cancer Institute)","place":["Montevideo, Uruguay"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina","family":"Barrios","sequence":"additional","affiliation":[{"name":"Instituto Nacional del C\u00e1ncer (National Cancer Institute)","place":["Montevideo, Uruguay"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio","family":"Cuello","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Hospital de Cl\u00ednicas","place":["Montevideo, Uruguay"]},{"name":"Instituto Nacional del C\u00e1ncer (National Cancer Institute)","place":["Montevideo, Uruguay"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1680838","article-title":"Combination of PD-1\/PD-L1 and CTLA-4 inhibitors in the treatment of cancer \u2013 a brief update","volume":"16","author":"Park","year":"2025","journal-title":"Front Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70412","article-title":"The role of immune checkpoint inhibitors in cancer therapy: mechanism and therapeutic advances","volume":"6","author":"Chen","year":"2025","journal-title":"MedComm"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-024-01581-2","article-title":"Dual blockade immunotherapy targeting PD-1\/PD-L1 and CTLA-4 in lung cancer","volume":"17","author":"Cheng","year":"2024","journal-title":"J Hematol Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16122223","article-title":"Clinical outcomes of immune checkpoint inhibitors in unique cohorts underrepresented in clinical trials","volume":"16","author":"Shah","year":"2024","journal-title":"Cancers (Basel)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1186\/s12916-020-01817-1","article-title":"Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies","volume":"18","author":"Cupp","year":"2020","journal-title":"BMC Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.52","article-title":"Neutrophils in cancer: neutral no more","volume":"16","author":"Coffelt","year":"2016","journal-title":"Nat Rev Cancer"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0222-4","article-title":"Tumour-associated neutrophils in patients with cancer","volume":"16","author":"Shaul","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S153290","article-title":"Prognostic utility of baseline neutrophil-to-lymphocyte ratio in patients receiving immune checkpoint inhibitors: a review and meta-analysis","volume":"11","author":"Sacdalan","year":"2018","journal-title":"Onco Targets Ther"},{"key":"B9","doi-asserted-by":"publisher","first-page":"106677","DOI":"10.1016\/j.intimp.2020.106677","article-title":"Predictive value of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in non-small cell lung cancer patients treated with immune checkpoint inhibitors: a meta-analysis","volume":"85","author":"Zhang","year":"2020","journal-title":"Int Immunopharmacol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1038\/s41467-021-20935-9","article-title":"Pretreatment neutrophil-to-lymphocyte ratio and mutational burden as biomarkers of tumor response to immune checkpoint inhibitors","volume":"12","author":"Valero","year":"2021","journal-title":"Nat Commun"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-019-02982-4","article-title":"Change in neutrophil to lymphocyte ratio during immunotherapy treatment is a non-linear predictor of patient outcomes in advanced cancers","volume":"145","author":"Li","year":"2019","journal-title":"J Cancer Res Clin Oncol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.lungcan.2020.04.027","article-title":"ECOG performance status \u22652 as a prognostic factor in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors\u2014a systematic review and meta-analysis of real-world data","volume":"145","author":"Bersanelli","year":"2020","journal-title":"Lung Cancer"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11121954","article-title":"EPSILoN: a prognostic score for immunotherapy in advanced non-small-cell lung cancer: a validation cohort","volume":"11","author":"Prelaj","year":"2019","journal-title":"Cancers (Basel)"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.28721","article-title":"Immune-mediated adverse events following atezolizumab and bevacizumab in a multinational Latin American cohort of unresectable hepatocellular carcinoma","volume":"16","author":"Gomes da Fonseca","year":"2025","journal-title":"Oncotarget"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1038\/s41598-020-79397-6","article-title":"Continuous monitoring of neutrophils to lymphocytes ratio for estimating the onset, severity, and subsequent prognosis of immune related adverse events","volume":"11","author":"Matsukane","year":"2021","journal-title":"Sci Rep"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aai7911","article-title":"Platelets subvert T cell immunity against cancer via GARP-TGF\u03b2 axis","volume":"2","author":"Rachidi","year":"2017","journal-title":"Sci Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190354","article-title":"Interleukin-17-induced neutrophil extracellular traps mediate resistance to checkpoint blockade in pancreatic cancer","volume":"217","author":"Zhang","year":"2020","journal-title":"J Exp Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.4771","article-title":"Association of the lung immune prognostic index with immune checkpoint inhibitor outcomes in patients with advanced non-small cell lung cancer","volume":"4","author":"Mezquita","year":"2018","journal-title":"JAMA Oncol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/j.2517-6161.1972.tb00899.x","article-title":"Regression models and life-tables","volume":"34","author":"Cox","year":"1972","journal-title":"J R Stat Soc Ser B Methodol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1958.10501452","article-title":"Nonparametric estimation from incomplete observations","volume":"53","author":"Kaplan","year":"1958","journal-title":"J Am Stat Assoc"},{"key":"B21","article-title":"Evaluation of survival data and two new rank order statistics arising in its consideration","volume":"50","author":"Mantel","year":"1966","journal-title":"Cancer Chemother Rep"},{"key":"B22","doi-asserted-by":"publisher","first-page":"73","DOI":"10.2307\/2532740","article-title":"Maximally selected rank statistics","volume":"48","author":"Lausen","year":"1992","journal-title":"Biometrics"},{"key":"B23","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1148\/radiology.143.1.7063747","article-title":"The meaning and use of the area under a receiver operating characteristic (ROC) curve","volume":"143","author":"Hanley","year":"1982","journal-title":"Radiology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Soc Ser B Methodol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1097\/00000421-198212000-00014","article-title":"Toxicity and response criteria of the Eastern Cooperative Oncology Group","volume":"5","author":"Oken","year":"1982","journal-title":"Am J Clin Oncol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910836","article-title":"Five-year survival with combined nivolumab and ipilimumab in advanced melanoma","volume":"381","author":"Larkin","year":"2019","journal-title":"N Engl J Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1712126","article-title":"Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma","volume":"378","author":"Motzer","year":"2018","journal-title":"N Engl J Med"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1930031\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:11:02Z","timestamp":1789654262000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1930031\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":28,"alternative-id":["10.3389\/fonc.2026.1930031"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1930031","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]},"article-number":"1930031"}}