{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T03:37:50Z","timestamp":1793417870287,"version":"4.5.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This investigation seeks to examine the association between spleen volume and prognosis in cancer patients undergoing immune checkpoint inhibitor (ICI) treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a retrospective analysis involving 61 patients diagnosed with hepatocellular carcinoma (HCC) who received ICIs at our institution. We evaluated the relationship between baseline splenic volume and its changes during ICI therapy concerning overall survival (OS) and progression-free survival (PFS) using a log-rank test. To identify relevant literature, we searched databases such as PubMed, EMBASE, the Cochrane Library, and Google Scholar up until February 20, 2024. The primary metrics assessed were hazard ratios (HR) for both OS and PFS, with pooled estimates and corresponding 95% confidence intervals (CIs) calculated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Within our study population, findings demonstrated a significantly decreased OS (HR: 2.02, 95% CI: 1.08\u20133.77,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.027) and PFS (HR: 1.84, 95% CI: 1.05\u20133.21,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.032) in HCC patients with a high baseline spleen volume, compared to individuals with lower spleen volumes. Additionally, HCC patients who experienced an increase in spleen volume during ICI therapy exhibited significantly poorer OS (HR: 2.27, 95% CI: 1.17\u20134.41,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.016) and PFS (HR: 2.40, 95% CI: 1.30\u20134.41,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.005) than those whose spleen volume decreased. The meta-analysis results revealed that subjects with higher spleen volumes had a significantly reduced OS (HR: 1.74, 95% CI: 1.12\u20132.72,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.014) and PFS (HR: 1.35, 95% CI: 1.15\u20131.58,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001) compared to counterparts with lower volumes. Furthermore, the data clearly highlighted that patients with increases in splenic volume faced significantly poorer clinical outcomes, as indicated by reduced OS (HR: 1.83, 95% CI: 1.36\u20132.46,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001) and PFS (HR: 1.70, 95% CI: 1.28\u20132.25,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001) relative to those with decreases in splenic size.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A higher baseline spleen volume and an increase in spleen volume during ICI therapy were predictors of a poor prognosis in cancer patients treated with ICI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1598484","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T01:47:38Z","timestamp":1748569658000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Splenic volume as a predictor of survival in cancer patients treated with immune checkpoint inhibitors"],"prefix":"10.3389","volume":"16","author":[{"given":"Yunhua","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.951137","article-title":"Integration of transcriptomics, proteomics, and metabolomics data to reveal HER2-associated metabolic heterogeneity in gastric cancer with response to immunotherapy and neoadjuvant chemotherapy","volume":"13","author":"Yuan","year":"2022","journal-title":"Front Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3239","article-title":"The blockade of immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"B4","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":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1411087","article-title":"PD-1 blockade with nivolumab in relapsed or refractory Hodgkin\u2019s lymphoma","volume":"372","author":"Ansell","year":"2015","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1056\/NEJMoa1504030","article-title":"Combined nivolumab and ipilimumab or monotherapy in untreated melanoma","volume":"373","author":"Larkin","year":"2015","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/s41389-017-0013-7","article-title":"Unwrapping the genomic characteristics of urothelial bladder cancer and successes with immune checkpoint blockade therapy","volume":"7","author":"Cheng","year":"2018","journal-title":"Oncogenesis"},{"key":"B8","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1186\/s12903-024-04252-3","article-title":"F. Nucleatum enhances oral squamous cell carcinoma proliferation via E-cadherin\/\u03b2-Catenin pathway","volume":"24","author":"Li","year":"2024","journal-title":"BMC  Health"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar4060","article-title":"Cancer immunotherapy using checkpoint blockade","volume":"359","author":"Ribas","year":"2018","journal-title":"Science"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-018-0142-8","article-title":"Cancer immunoediting and resistance to T cell-based immunotherapy","volume":"16","author":"O\u2019Donnell","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.0726","article-title":"Immune checkpoint inhibitor rechallenge after immune-related adverse events in patients with cancer","volume":"6","author":"Dolladille","year":"2020","journal-title":"JAMA Oncol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"110019","DOI":"10.1016\/j.intimp.2023.110019","article-title":"Blood biomarkers predict outcomes in patients with hepatocellular carcinoma treated with immune checkpoint Inhibitors: A pooled analysis of 44 retrospective sudies","volume":"118","author":"Zhang","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1083840","article-title":"Nomogram for predicting prognosis of patients with metastatic melanoma after immunotherapy: A Chinese population-based analysis","volume":"13","author":"Zhao","year":"2022","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2021.1951522","article-title":"Identification and validation of a novel redox-related lncRNA prognostic signature in lung adenocarcinoma","volume":"12","author":"Ren","year":"2021","journal-title":"Bioengineered"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0116-x","article-title":"The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy","volume":"19","author":"Havel","year":"2019","journal-title":"Nat Rev Cancer"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-2085","article-title":"Spatial and Temporal Heterogeneity of PD-L1 Expression and Tumor Mutational Burden in Gastroesophageal Adenocarcinoma at Baseline Diagnosis and after Chemotherapy","volume":"26","author":"Zhou","year":"2020","journal-title":"Clin Cancer Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2016.10.013","article-title":"Companion and complementary diagnostics: clinical and regulatory perspectives","volume":"2","author":"J\u00f8rgensen","year":"2016","journal-title":"Trends Cancer"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0856-x","article-title":"Elevated serum interleukin-8 is associated with enhanced intratumor neutrophils and reduced clinical benefit of immune-checkpoint inhibitors","volume":"26","author":"Schalper","year":"2020","journal-title":"Nat Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1516362","article-title":"Immune-related diagnostic markers for benign prostatic hyperplasia and their potential as drug targets","volume":"15","author":"Wang","year":"2024","journal-title":"Front Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"897","DOI":"10.17305\/bb.2024.9979","article-title":"JAM3: A prognostic biomarker for bladder cancer via epithelial-mesenchymal transition regulation","volume":"24","author":"Pang","year":"2024","journal-title":"Biomol Biomed"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s003300050145","article-title":"Determination of normal splenic volume on computed tomography in relation to age, gender and body habitus","volume":"7","author":"Prassopoulos","year":"1997","journal-title":"Eur Radiol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"106784","DOI":"10.1016\/j.micpath.2024.106784","article-title":"Changes in the gut microbiome of patients with esophageal cancer: A systematic review and meta-analysis based on 16S gene sequencing technology","volume":"193","author":"Deng","year":"2024","journal-title":"Microb Pathog"},{"key":"B23","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.clnu.2023.11.009","article-title":"Sarcopenia affects the clinical efficacy of immune checkpoint inhibitors in patients with gastrointestinal cancers","volume":"43","author":"Lilong","year":"2024","journal-title":"Clin Nutr"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in meta-analysis detected by a simple, graphical test","volume":"315","author":"Egger","year":"1997","journal-title":"Bmj"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.2307\/2533446","article-title":"Operating characteristics of a rank correlation test for publication bias","volume":"50","author":"Begg","year":"1994","journal-title":"Biometrics"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000001864","article-title":"Influence of body fat tissue on outcomes in patients undergoing hepatectomy or liver transplantation: a systematic review and meta-analysis","volume":"111","author":"Zhang","year":"2025","journal-title":"Int J Surg"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13123020","article-title":"Splenic volume as a surrogate marker of immune checkpoint inhibitor efficacy in metastatic non small cell lung cancer","volume":"13","author":"Galland","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1973710","DOI":"10.1080\/2162402X.2021.1973710","article-title":"Negative prognostic implications of splenomegaly in nivolumab-treated advanced or recurrent pancreatic adenocarcinoma","volume":"10","author":"Yang","year":"2021","journal-title":"Oncoimmunology"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14153574","article-title":"Baseline splenic volume outweighs immuno-modulated size changes with regard to survival outcome in patients with hepatocellular carcinoma under immunotherapy","volume":"14","author":"M\u00fcller","year":"2022","journal-title":"Cancers"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.v11.24","article-title":"Splenomegaly in predicting the survival of patients with advanced primary liver cancer treated with immune checkpoint inhibitors","volume":"11","author":"Xiao","year":"2022","journal-title":"Cancer Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1186\/s12885-023-11558-y","article-title":"The role of spleen volume change in predicting immunotherapy response in metastatic renal cell carcinoma","volume":"23","author":"Aslan","year":"2023","journal-title":"BMC Cancer"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11092482","article-title":"Change in splenic volume as a surrogate marker for immunotherapy response in patients with advanced urothelial and renal cell carcinoma-evaluation of a novel approach of fully automated artificial intelligence based splenic segmentation","volume":"11","author":"Duwe","year":"2023","journal-title":"Biomedicines"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2022-0222","article-title":"Imaging-calculated splenic volume is associated with response in melanoma patients treated with immunotherapy","volume":"15","author":"Oliveira Taveira","year":"2023","journal-title":"Immunotherapy"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1159\/000541002","article-title":"Factors affecting an increase in spleen volume and association of spleen volume variation with the clinical outcomes of atezolizumab and bevacizumab treatment for hepatocellular carcinoma: A retrospective analysis","volume":"103","author":"Hatanaka","year":"2024","journal-title":"Oncology"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-008191","article-title":"Prognostic model for unresectable hepatocellular carcinoma treated with dual PD-1 and angiogenesis blockade therapy","volume":"12","author":"Mo","year":"2024","journal-title":"J Immunother Cancer"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2723264","DOI":"10.1155\/2022\/2723264","article-title":"IL1RN and PRRX1 as a prognostic biomarker correlated with immune infiltrates in colorectal cancer: evidence from bioinformatic analysis","volume":"2022","author":"Wang","year":"2022","journal-title":"Int J Genomics"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.010","article-title":"The spleen in local and systemic regulation of immunity","volume":"39","author":"Bronte","year":"2013","journal-title":"Immunity"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00529.x","article-title":"Signal transduction of MCP-1 expression induced by pancreatitis-associated ascitic fluid in pancreatic acinar cells","volume":"13","author":"Ramudo","year":"2009","journal-title":"J Cell Mol Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-3164","article-title":"Accumulation of MDSC and th17 cells in patients with metastatic colorectal cancer predicts the efficacy of a FOLFOX-bevacizumab drug treatment regimen","volume":"76","author":"Limagne","year":"2016","journal-title":"Cancer Res"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.926230","article-title":"The role of adipokines in pancreatic cancer","volume":"12","author":"Wang","year":"2022","journal-title":"Front Oncol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1158\/2326-6066.CIR-16-0297","article-title":"Myeloid-derived suppressor cells","volume":"5","author":"Gabrilovich","year":"2017","journal-title":"Cancer Immunol Res"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001895","article-title":"Blocking IL-17A enhances tumor response to anti-PD-1 immunotherapy in microsatellite stable colorectal cancer","volume":"9","author":"Liu","year":"2021","journal-title":"J Immunother Cancer"},{"key":"B43","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/s00005-018-0531-9","article-title":"Roles of myeloid-derived suppressor cells in cancer metastasis: immunosuppression and beyond","volume":"67","author":"Pastaki Khoshbin","year":"2019","journal-title":"Arch Immunol Ther Exp (Warsz)"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-00490-y","article-title":"Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity","volume":"21","author":"Veglia","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1236435","article-title":"Single-cell RNA sequencing identifies a novel proliferation cell type affecting clinical outcome of pancreatic ductal adenocarcinoma","volume":"13","author":"Ye","year":"2023","journal-title":"Front Oncol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-024-03697-w","article-title":"Tumor microenvironment as a complex milieu driving cancer progression: a mini review","volume":"27","author":"Li","year":"2024","journal-title":"Clin Transl Oncol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"237ra67","DOI":"10.1126\/scitranslmed.3007974","article-title":"Disruption of CXCR2-mediated MDSC tumor trafficking enhances anti-PD1 efficacy","volume":"6","author":"Highfill","year":"2014","journal-title":"Sci Transl Med"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1172\/JCI90499","article-title":"Treg depletion potentiates checkpoint inhibition in claudin-low breast cancer","volume":"127","author":"Taylor","year":"2017","journal-title":"J Clin Invest"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-2267","article-title":"Primary and acquired resistance to immune checkpoint inhibitors in metastatic melanoma","volume":"24","author":"Gide","year":"2018","journal-title":"Clin Cancer Res"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2815","article-title":"In vivo margin assessment during partial mastectomy breast surgery using raman spectroscopy","volume":"66","author":"Haka","year":"2006","journal-title":"Cancer Res"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-322196","article-title":"High-affinity neoantigens correlate with better prognosis and trigger potent antihepatocellular carcinoma (HCC) activity by activating CD39(+)CD8(+) T cells","volume":"70","author":"Liu","year":"2021","journal-title":"Gut"},{"key":"B52","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/s12943-017-0712-x","article-title":"The biology of Hepatocellular carcinoma: implications for genomic and immune therapies","volume":"16","author":"Khemlina","year":"2017","journal-title":"Mol Cancer"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.v149.4","article-title":"Immune-related adverse events predict responses to PD-1 blockade immunotherapy in hepatocellular carcinoma","volume":"149","author":"Lu","year":"2021","journal-title":"Int J Cancer"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1598484\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T01:47:39Z","timestamp":1748569659000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1598484\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,30]]},"references-count":53,"alternative-id":["10.3389\/fimmu.2025.1598484"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1598484","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,30]]},"article-number":"1598484"}}