{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:19:58Z","timestamp":1790741998993,"version":"4.1.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Guizhou Provincial Science and Technology Projects","award":["Qiankehe Fundamentals-ZK(2024)-General 202"],"award-info":[{"award-number":["Qiankehe Fundamentals-ZK(2024)-General 202"]}]},{"DOI":"10.13039\/100017957","name":"Health Commission of Guizhou Province","doi-asserted-by":"publisher","award":["2024-204"],"award-info":[{"award-number":["2024-204"]}],"id":[{"id":"10.13039\/100017957","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guizhou Medical University National Foundation Cultivation Project","award":["21NSFCP15"],"award-info":[{"award-number":["21NSFCP15"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82360588"],"award-info":[{"award-number":["82360588"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Cervical cancer (CC) is a leading cause of cancer-related mortality among women and is strongly associated with persistent infection by high-risk human papillomavirus (HR-HPV), particularly the HPV16 subtype. Existing detection methods have limitations in meeting clinical requirements. This study aims to identify biomarkers that can aid in the staging and prognosis of cervical cancer. Cervical epithelial exfoliated cell samples were collected from three groups: HPV16-negative normal cervix, HPV16-positive normal cervix, and HPV16-positive cervical cancer. Differential expression proteins (DEPs) were identified using TMT-LC\u2013MS\/MS technology, and their associations with tumor-infiltrating lymphocytes (TILs) and immune regulatory molecules were analyzed. Leukocyte-specific protein 1 (LSP1), an intracellular F-actin-binding protein predominantly expressed in macrophages, neutrophils, B cells, and T cells, was identified as a potential biomarker. The expression levels of LSP1 were evaluated and validated using the Human Protein Atlas (HPA) database, immunohistochemistry (IHC), Western blotting (WB), and real-time quantitative PCR (RT-qPCR). Multiplex fluorescence immunohistochemistry (mIHC) was employed to assess the co-localization of LSP1 with CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells. Results indicated that both protein and mRNA levels of LSP1 were significantly elevated in cervical cancer tissues compared to adjacent non-tumor tissues. Notably, LSP1 expression was higher in early-stage cervical cancer (Stage IB) than in advanced-stage disease (Stage IIIC). Furthermore, LSP1 was predominantly localized in CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells with low TIM-3 expression. Analysis of public databases (GEPIA, TIMER2.0, and TISIDB) revealed that higher LSP1 mRNA levels correlated with better patient outcomes. LSP1 expression was positively associated with the abundance of major TILs and immune regulatory molecules, particularly activated B cells, CD8<jats:sup>+<\/jats:sup> T cells, and CD4<jats:sup>+<\/jats:sup> T cells, while negatively correlated with M2 macrophages and myeloid-derived suppressor cells. These findings indicate that the expression levels of LSP1 in cervical tissues are correlated with cancer staging and patient prognosis, potentially reflecting both tumor immune infiltration and T-cell exhaustion within the tumor microenvironment (TME).<\/jats:p>","DOI":"10.1038\/s41598-025-91066-0","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T07:33:56Z","timestamp":1741073636000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Leukocyte-specific protein 1 is associated with the stage and tumor immune infiltration of cervical cancer"],"prefix":"10.1038","volume":"15","author":[{"given":"Dianqin","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinzhu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoju","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luhong","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yameng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwen","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3021-0039","authenticated-orcid":false,"given":"Yujie","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,4]]},"reference":[{"key":"91066_CR1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1136\/ijgc-2022-003703","volume":"33","author":"D Viveros-Carreno","year":"2023","unstructured":"Viveros-Carreno, D., Fernandes, A. & Pareja, R. Updates on cervical cancer prevention. Int. J. Gynecol. Cancer 33, 394\u2013402. https:\/\/doi.org\/10.1136\/ijgc-2022-003703 (2023).","journal-title":"Int. J. Gynecol. Cancer"},{"key":"91066_CR2","unstructured":"Mello, V. & Sundstrom, R. K. in StatPearls (2023)."},{"key":"91066_CR3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/s40364-022-00428-7","volume":"10","author":"Q Sun","year":"2022","unstructured":"Sun, Q., Wang, L., Zhang, C., Hong, Z. & Han, Z. Cervical cancer heterogeneity: A constant battle against viruses and drugs. Biomark Res. 10, 85. https:\/\/doi.org\/10.1186\/s40364-022-00428-7 (2022).","journal-title":"Biomark Res."},{"key":"91066_CR4","doi-asserted-by":"publisher","first-page":"3116","DOI":"10.3389\/fmicb.2019.03116","volume":"10","author":"A Pal","year":"2019","unstructured":"Pal, A. & Kundu, R. Human papillomavirus E6 and E7: The cervical cancer hallmarks and targets for therapy. Front. Microbiol. 10, 3116. https:\/\/doi.org\/10.3389\/fmicb.2019.03116 (2019).","journal-title":"Front. Microbiol."},{"key":"91066_CR5","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.7150\/jca.17120","volume":"8","author":"J Peng","year":"2017","unstructured":"Peng, J. et al. Cervical cancers manifest a high rate of infection by a high-risk human papilloma virus subtype but a very low rate of infection by a low-risk subtype in the Guiyang District of China. J. Cancer 8, 1263\u20131270. https:\/\/doi.org\/10.7150\/jca.17120 (2017).","journal-title":"J. Cancer"},{"key":"91066_CR6","doi-asserted-by":"publisher","first-page":"2959","DOI":"10.1099\/0022-1317-81-12-2959","volume":"81","author":"LL Villa","year":"2000","unstructured":"Villa, L. L. et al. Molecular variants of human papillomavirus types 16 and 18 preferentially associated with cervical neoplasia. J. Gen. Virol. 81, 2959\u20132968. https:\/\/doi.org\/10.1099\/0022-1317-81-12-2959 (2000).","journal-title":"J. Gen. Virol."},{"key":"91066_CR7","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/sj.bjc.6602915","volume":"94","author":"S Bulk","year":"2006","unstructured":"Bulk, S. et al. Preferential risk of HPV16 for squamous cell carcinoma and of HPV18 for adenocarcinoma of the cervix compared to women with normal cytology in the Netherlands. Br. J. Cancer 94, 171\u2013175. https:\/\/doi.org\/10.1038\/sj.bjc.6602915 (2006).","journal-title":"Br. J. Cancer"},{"key":"91066_CR8","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1186\/s12905-020-01035-0","volume":"20","author":"RL da Silva","year":"2020","unstructured":"da Silva, R. L. et al. Role of HPV 16 variants among cervical carcinoma samples from Northeastern Brazil. BMC Womens Health 20, 162. https:\/\/doi.org\/10.1186\/s12905-020-01035-0 (2020).","journal-title":"BMC Womens Health"},{"key":"91066_CR9","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics13020243","author":"O Illah","year":"2023","unstructured":"Illah, O. & Olaitan, A. Updates on HPV vaccination. Diagnostics (Basel) https:\/\/doi.org\/10.3390\/diagnostics13020243 (2023).","journal-title":"Diagnostics (Basel)"},{"key":"91066_CR10","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1158\/1055-9965.EPI-12-1406","volume":"22","author":"M Schiffman","year":"2013","unstructured":"Schiffman, M. & Wentzensen, N. Human papillomavirus infection and the multistage carcinogenesis of cervical cancer. Cancer Epidemiol. Biomark. Prev. 22, 553\u2013560. https:\/\/doi.org\/10.1158\/1055-9965.EPI-12-1406 (2013).","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"91066_CR11","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1158\/2159-8290.CD-20-1760","volume":"11","author":"AA Shamseddine","year":"2021","unstructured":"Shamseddine, A. A., Burman, B., Lee, N. Y., Zamarin, D. & Riaz, N. Tumor immunity and immunotherapy for HPV-related cancers. Cancer Discov. 11, 1896\u20131912. https:\/\/doi.org\/10.1158\/2159-8290.CD-20-1760 (2021).","journal-title":"Cancer Discov."},{"key":"91066_CR12","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1158\/1078-0432.ccr-14-1860","volume":"21","author":"GL Beatty","year":"2015","unstructured":"Beatty, G. L. & Gladney, W. L. Immune escape mechanisms as a guide for cancer immunotherapy. Clin. Cancer Res.: Offic. J. Am. Assoc. Cancer Res. 21, 687\u2013692. https:\/\/doi.org\/10.1158\/1078-0432.ccr-14-1860 (2015).","journal-title":"Clin. Cancer Res.: Offic. J. Am. Assoc. Cancer Res."},{"key":"91066_CR13","doi-asserted-by":"publisher","first-page":"5317","DOI":"10.1038\/ncomms6317","volume":"5","author":"TJ Kim","year":"2014","unstructured":"Kim, T. J. et al. Clearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients. Nat. Commun. 5, 5317. https:\/\/doi.org\/10.1038\/ncomms6317 (2014).","journal-title":"Nat. Commun."},{"key":"91066_CR14","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.1007\/s00262-022-03350-x","volume":"72","author":"SJ Santegoets","year":"2023","unstructured":"Santegoets, S. J. et al. The common HLA class I-restricted tumor-infiltrating T cell response in HPV16-induced cancer. Cancer Immunol. Immunother. 72, 1553\u20131565. https:\/\/doi.org\/10.1007\/s00262-022-03350-x (2023).","journal-title":"Cancer Immunol. Immunother."},{"key":"91066_CR15","doi-asserted-by":"publisher","first-page":"4953","DOI":"10.1158\/1078-0432.CCR-20-2833","volume":"27","author":"L Ferrall","year":"2021","unstructured":"Ferrall, L., Lin, K. Y., Roden, R. B. S., Hung, C. F. & Wu, T. C. Cervical cancer immunotherapy: Facts and hopes. Clin. Cancer Res.: Offic. J. Am. Assoc. Cancer Res. 27, 4953\u20134973. https:\/\/doi.org\/10.1158\/1078-0432.CCR-20-2833 (2021).","journal-title":"Clin. Cancer Res.: Offic. J. Am. Assoc. Cancer Res."},{"key":"91066_CR16","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13092089","author":"S Duranti","year":"2021","unstructured":"Duranti, S. et al. Role of immune checkpoint inhibitors in cervical cancer: From Preclinical to clinical data. Cancers (Basel) https:\/\/doi.org\/10.3390\/cancers13092089 (2021).","journal-title":"Cancers (Basel)"},{"key":"91066_CR17","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.ccell.2017.02.008","volume":"31","author":"KG Anderson","year":"2017","unstructured":"Anderson, K. G., Stromnes, I. M. & Greenberg, P. D. Obstacles posed by the tumor microenvironment to T cell activity: A case for synergistic therapies. Cancer Cell 31, 311\u2013325. https:\/\/doi.org\/10.1016\/j.ccell.2017.02.008 (2017).","journal-title":"Cancer Cell"},{"key":"91066_CR18","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1091\/mbc.E14-05-1005","volume":"26","author":"S Maxeiner","year":"2015","unstructured":"Maxeiner, S. et al. Crucial role for the LSP1-myosin1e bimolecular complex in the regulation of Fc\u03b3 receptor-driven phagocytosis. Mol. Biol. Cell 26, 1652\u20131664. https:\/\/doi.org\/10.1091\/mbc.E14-05-1005 (2015).","journal-title":"Mol. Biol. Cell"},{"key":"91066_CR19","doi-asserted-by":"publisher","first-page":"291","DOI":"10.29252\/rbmb.9.3.291","volume":"9","author":"Z Nourolahzadeh","year":"2020","unstructured":"Nourolahzadeh, Z., Houshmand, M., Mohammad, F. M. & Ghorbian, S. Correlation between Lsp1 (Rs3817198) and Casc (Rs4784227) polymorphisms and the susceptibility to breast cancer. Rep. Biochem. Mol. Biol. 9, 291\u2013296. https:\/\/doi.org\/10.29252\/rbmb.9.3.291 (2020).","journal-title":"Rep. Biochem. Mol. Biol."},{"key":"91066_CR20","doi-asserted-by":"publisher","first-page":"63960","DOI":"10.18632\/oncotarget.11741","volume":"7","author":"J Tang","year":"2016","unstructured":"Tang, J. et al. The LSP1 rs3817198 T > C polymorphism contributes to increased breast cancer risk: A meta-analysis of twelve studies. Oncotarget 7, 63960\u201363967. https:\/\/doi.org\/10.18632\/oncotarget.11741 (2016).","journal-title":"Oncotarget"},{"key":"91066_CR21","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1016\/j.ajpath.2011.12.021","volume":"180","author":"MA Nalesnik","year":"2012","unstructured":"Nalesnik, M. A. et al. Gene deletions and amplifications in human hepatocellular carcinomas: correlation with hepatocyte growth regulation. Am. J. Pathol. 180, 1495\u20131508. https:\/\/doi.org\/10.1016\/j.ajpath.2011.12.021 (2012).","journal-title":"Am. J. Pathol."},{"key":"91066_CR22","doi-asserted-by":"publisher","first-page":"6580","DOI":"10.1158\/1078-0432.ccr-17-0033","volume":"23","author":"SX Zeng","year":"2017","unstructured":"Zeng, S. X. et al. The phosphatidylinositol 3-kinase pathway as a potential therapeutic target in bladder cancer. Clin. Cancer Res.: Offic. J. Am. Assoc. Cancer Res. 23, 6580\u20136591. https:\/\/doi.org\/10.1158\/1078-0432.ccr-17-0033 (2017).","journal-title":"Clin. Cancer Res.: Offic. J. Am. Assoc. Cancer Res."},{"key":"91066_CR23","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1002\/hep.27444","volume":"61","author":"K Koral","year":"2015","unstructured":"Koral, K. et al. Leukocyte-specific protein 1: A novel regulator of hepatocellular proliferation and migration deleted in human hepatocellular carcinoma. Hepatology 61, 537\u2013547. https:\/\/doi.org\/10.1002\/hep.27444 (2015).","journal-title":"Hepatology"},{"key":"91066_CR24","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/j.ajpath.2022.03.010","volume":"192","author":"K Koral","year":"2022","unstructured":"Koral, K. et al. Lymphocyte-specific protein-1 suppresses xenobiotic-induced constitutive androstane receptor and subsequent yes-associated protein-activated hepatocyte proliferation. Am. J. Pathol. 192, 887\u2013903. https:\/\/doi.org\/10.1016\/j.ajpath.2022.03.010 (2022).","journal-title":"Am. J. Pathol."},{"key":"91066_CR25","doi-asserted-by":"publisher","first-page":"1656","DOI":"10.18632\/aging.102706","volume":"12","author":"JY Cao","year":"2020","unstructured":"Cao, J. Y. et al. Elevated lymphocyte specific protein 1 expression is involved in the regulation of leukocyte migration and immunosuppressive microenvironment in glioblastoma. Aging (Albany NY) 12, 1656\u20131684. https:\/\/doi.org\/10.18632\/aging.102706 (2020).","journal-title":"Aging (Albany NY)"},{"key":"91066_CR26","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001180","author":"R Kwon","year":"2020","unstructured":"Kwon, R. et al. Regulation of tumor growth by leukocyte-specific protein 1 in T cells. J. Immunother. Cancer https:\/\/doi.org\/10.1136\/jitc-2020-001180 (2020).","journal-title":"J. Immunother. Cancer"},{"key":"91066_CR27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2021.104453","volume":"252","author":"D Xu","year":"2022","unstructured":"Xu, D. et al. Quantitative proteomic analysis of cervical cancer based on TMT-labeled quantitative proteomics. J. Proteomics 252, 104453. https:\/\/doi.org\/10.1016\/j.jprot.2021.104453 (2022).","journal-title":"J. Proteomics"},{"key":"91066_CR28","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000740RR","volume":"35","author":"K Sch\u00e4ringer","year":"2021","unstructured":"Sch\u00e4ringer, K. et al. LSP1-myosin1e bimolecular complex regulates focal adhesion dynamics and cell migration. FASEB J.: Offic. Pub. Fed. Am. Soc. Exp. Biol. 35, e21268. https:\/\/doi.org\/10.1096\/fj.202000740RR (2021).","journal-title":"FASEB J.: Offic. Pub. Fed. Am. Soc. Exp. Biol."},{"key":"91066_CR29","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000528RR","volume":"35","author":"Z Chen","year":"2021","unstructured":"Chen, Z., Dong, D., Zhu, Y., Pang, N. & Ding, J. The role of Tim-3\/Galectin-9 pathway in T-cell function and prognosis of patients with human papilloma virus-associated cervical carcinoma. FASEB J. 35, e21401. https:\/\/doi.org\/10.1096\/fj.202000528RR (2021).","journal-title":"FASEB J."},{"key":"91066_CR30","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-000911","author":"N Acharya","year":"2020","unstructured":"Acharya, N., Sabatos-Peyton, C. & Anderson, A. C. Tim-3 finds its place in the cancer immunotherapy landscape. J. Immunother. Cancer https:\/\/doi.org\/10.1136\/jitc-2020-000911 (2020).","journal-title":"J. Immunother. Cancer"},{"key":"91066_CR31","doi-asserted-by":"publisher","DOI":"10.1136\/esmoopen-2019-000629","volume":"4","author":"AM Starzer","year":"2020","unstructured":"Starzer, A. M. & Berghoff, A. S. New emerging targets in cancer immunotherapy: CD27 (TNFRSF7). ESMO Open 4, e000629. https:\/\/doi.org\/10.1136\/esmoopen-2019-000629 (2020).","journal-title":"ESMO Open"},{"key":"91066_CR32","doi-asserted-by":"publisher","DOI":"10.4110\/in.2020.20.e3","volume":"20","author":"S Jeong","year":"2020","unstructured":"Jeong, S. & Park, S. H. Co-Stimulatory receptors in cancers and their implications for cancer immunotherapy. Immune Netw. 20, e3. https:\/\/doi.org\/10.4110\/in.2020.20.e3 (2020).","journal-title":"Immune Netw."},{"key":"91066_CR33","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1038\/s41416-021-01400-2","volume":"125","author":"E Schaafsma","year":"2021","unstructured":"Schaafsma, E., Fugle, C. M., Wang, X. & Cheng, C. Pan-cancer association of HLA gene expression with cancer prognosis and immunotherapy efficacy. Br. J. Cancer 125, 422\u2013432. https:\/\/doi.org\/10.1038\/s41416-021-01400-2 (2021).","journal-title":"Br. J. Cancer"},{"key":"91066_CR34","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1186\/s12935-021-02101-9","volume":"21","author":"W Kong","year":"2021","unstructured":"Kong, W. et al. Analysis of therapeutic targets and prognostic biomarkers of CXC chemokines in cervical cancer microenvironment. Cancer Cell Int. 21, 399. https:\/\/doi.org\/10.1186\/s12935-021-02101-9 (2021).","journal-title":"Cancer Cell Int."},{"key":"91066_CR35","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1007\/s12272-018-1015-5","volume":"41","author":"Y Jin","year":"2018","unstructured":"Jin, Y. et al. Use of protein-based biomarkers of exfoliated cervical cells for primary screening of cervical cancer. Arch. Pharm. Res. 41, 438\u2013449. https:\/\/doi.org\/10.1007\/s12272-018-1015-5 (2018).","journal-title":"Arch. Pharm. Res."},{"key":"91066_CR36","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1093\/chromsci\/bmu039","volume":"53","author":"S Bhat","year":"2015","unstructured":"Bhat, S., Kartha, V. B., Rai, L. & Chidangil, S. A comparison of protein profiles of cervical tissue homogenate, exfoliated cells from cervix and serum in normal and cervical malignancy conditions. J. Chromatogr. Sci. 53, 167\u2013176. https:\/\/doi.org\/10.1093\/chromsci\/bmu039 (2015).","journal-title":"J. Chromatogr. Sci."},{"key":"91066_CR37","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1186\/s13046-019-1153-8","volume":"38","author":"CK Looi","year":"2019","unstructured":"Looi, C. K. et al. Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment. J. Exp. Clin. Cancer Res. 38, 162. https:\/\/doi.org\/10.1186\/s13046-019-1153-8 (2019).","journal-title":"Journal of Experimental \uff06 Clinical Cancer Research."},{"key":"91066_CR38","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05672-3","author":"M Sorin","year":"2023","unstructured":"Sorin, M., Rezanejad, M., Karimi, E. & Fiset, B. Single-cell spatial landscapes of the lung tumour immune microenvironment. Nature https:\/\/doi.org\/10.1038\/s41586-022-05672-3 (2023).","journal-title":"Nature"},{"key":"91066_CR39","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1038\/s41416-020-01184-x","volume":"124","author":"TR Litwin","year":"2021","unstructured":"Litwin, T. R. et al. Infiltrating T-cell markers in cervical carcinogenesis: A systematic review and meta-analysis. Br. J. Cancer 124, 831\u2013841. https:\/\/doi.org\/10.1038\/s41416-020-01184-x (2021).","journal-title":"Br. J. Cancer"},{"key":"91066_CR40","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.21037\/tlcr-24-379","volume":"13","author":"J Zhao","year":"2024","unstructured":"Zhao, J. et al. Tumor immune microenvironment analysis of non-small cell lung cancer development through multiplex immunofluorescence. Transl. Lung Cancer Res. 13, 2395\u20132410. https:\/\/doi.org\/10.21037\/tlcr-24-379 (2024).","journal-title":"Transl. Lung Cancer Res."},{"key":"91066_CR41","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1002\/2211-5463.12079","volume":"6","author":"H Liu","year":"2016","unstructured":"Liu, H., Zhi, L., Duan, N. & Su, P. Abnormal expression of Tim-3 antigen on peripheral blood T cells is associated with progressive disease in osteosarcoma patients. FEBS Open Bio 6, 807\u2013815. https:\/\/doi.org\/10.1002\/2211-5463.12079 (2016).","journal-title":"FEBS Open Bio"},{"key":"91066_CR42","doi-asserted-by":"publisher","first-page":"107327482412742","DOI":"10.1177\/10732748241274228","volume":"31","author":"X Wang","year":"2024","unstructured":"Wang, X. et al. Integrating Single-Cell RNA-Seq and Bulk RNA-Seq to Construct a Novel \u03b3\u03b4T Cell-Related Prognostic Signature for Human Papillomavirus-Infected Cervical Cancer. Cancer Control 31, 10732748241274228. https:\/\/doi.org\/10.1177\/10732748241274228 (2024).","journal-title":"Cancer Control"},{"key":"91066_CR43","doi-asserted-by":"publisher","first-page":"8037","DOI":"10.2147\/OTT.S264312","volume":"13","author":"L Guo","year":"2020","unstructured":"Guo, L. & Hua, K. Cervical cancer: Emerging immune landscape and treatment. Onco Targets Ther. 13, 8037\u20138047. https:\/\/doi.org\/10.2147\/OTT.S264312 (2020).","journal-title":"Onco Targets Ther."},{"key":"91066_CR44","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.1182\/blood.V96.5.1827","volume":"96","author":"J Jongstra-Bilen","year":"2000","unstructured":"Jongstra-Bilen, J. et al. LSP1 modulates leukocyte populations in resting and inflamed peritoneum. Blood 96, 1827\u20131835 (2000).","journal-title":"Blood"},{"key":"91066_CR45","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1038\/s41467-018-02904-x","volume":"9","author":"P Cervero","year":"2018","unstructured":"Cervero, P., Wiesner, C., Bouissou, A., Poincloux, R. & Linder, S. Lymphocyte-specific protein 1 regulates mechanosensory oscillation of podosomes and actin isoform-based actomyosin symmetry breaking. Nat. Commun. 9, 515. https:\/\/doi.org\/10.1038\/s41467-018-02904-x (2018).","journal-title":"Nat. Commun."},{"key":"91066_CR46","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/s41577-022-00707-2","volume":"22","author":"N Pishesha","year":"2022","unstructured":"Pishesha, N., Harmand, T. J. & Ploegh, H. L. A guide to antigen processing and presentation. Nat. Rev. Immunol. 22, 751\u2013764. https:\/\/doi.org\/10.1038\/s41577-022-00707-2 (2022).","journal-title":"Nature Reviews. Immunology."},{"key":"91066_CR47","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.757137","volume":"10","author":"R Yi","year":"2022","unstructured":"Yi, R. et al. MHC-II signature correlates with Anti-Tumor immunity and predicts anti-PD-L1 response of bladder cancer. Front. Cell Dev. Biol. 10, 757137. https:\/\/doi.org\/10.3389\/fcell.2022.757137 (2022).","journal-title":"Front. Cell Dev. Biol."},{"key":"91066_CR48","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/s41586-021-03626-9","volume":"595","author":"KO Dixon","year":"2021","unstructured":"Dixon, K. O. et al. TIM-3 restrains anti-tumour immunity by regulating inflammasome activation. Nature 595, 101\u2013106. https:\/\/doi.org\/10.1038\/s41586-021-03626-9 (2021).","journal-title":"Nature"},{"key":"91066_CR49","doi-asserted-by":"publisher","first-page":"L995","DOI":"10.1152\/ajplung.00068.2014","volume":"309","author":"NP Le","year":"2015","unstructured":"Le, N. P., Channabasappa, S., Hossain, M., Liu, L. & Singh, B. Leukocyte-specific protein 1 regulates neutrophil recruitment in acute lung inflammation. Am. J. Physiol. Lung Cell. Mol. Physiol. 309, L995-1008. https:\/\/doi.org\/10.1152\/ajplung.00068.2014 (2015).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"91066_CR50","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s12931-022-02078-7","volume":"23","author":"NPK Le","year":"2022","unstructured":"Le, N. P. K. et al. Deficiency of leukocyte-specific protein 1 (LSP1) alleviates asthmatic inflammation in a mouse model.. Respir. Res. 23, 165. https:\/\/doi.org\/10.1186\/s12931-022-02078-7 (2022).","journal-title":"Respir. Res."},{"key":"91066_CR51","doi-asserted-by":"publisher","DOI":"10.3390\/life12081284","author":"SP Hilchey","year":"2022","unstructured":"Hilchey, S. P. & Palshikar, M. G. Cyclosporine a modulates LSP1 protein levels in human B cells to attenuate B cell migration at low O(2) levels. Life https:\/\/doi.org\/10.3390\/life12081284 (2022).","journal-title":"Life"},{"key":"91066_CR52","doi-asserted-by":"publisher","first-page":"W509","DOI":"10.1093\/nar\/gkaa407","volume":"48","author":"T Li","year":"2020","unstructured":"Li, T. et al. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 48, W509\u2013W514. https:\/\/doi.org\/10.1093\/nar\/gkaa407 (2020).","journal-title":"Nucleic Acids Res."},{"key":"91066_CR53","doi-asserted-by":"publisher","first-page":"4200","DOI":"10.1093\/bioinformatics\/btz210","volume":"35","author":"B Ru","year":"2019","unstructured":"Ru, B. et al. TISIDB: An integrated repository portal for tumor-immune system interactions. Bioinform. (Oxford, England) 35, 4200\u20134202. https:\/\/doi.org\/10.1093\/bioinformatics\/btz210 (2019).","journal-title":"Bioinform. (Oxford, England)"},{"key":"91066_CR54","doi-asserted-by":"publisher","first-page":"W98","DOI":"10.1093\/nar\/gkx247","volume":"45","author":"Z Tang","year":"2017","unstructured":"Tang, Z. et al. GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 45, W98\u2013W102. https:\/\/doi.org\/10.1093\/nar\/gkx247 (2017).","journal-title":"Nucleic Acids Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-91066-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-91066-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-91066-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T07:34:04Z","timestamp":1741073644000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-91066-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,4]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["91066"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-91066-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,4]]},"assertion":[{"value":"4 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declaration"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study was conducted according to the guidelines of the Declaration of Helsinki and was approved by the Medical Ethics Committee of the Affiliated Hospital of Guizhou Medical University(2022 No.720). Patients were consented by an informed consent process that was reviewed by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University and informed consent was obtained from all patients and\/or their legal guardians.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}],"article-number":"7566"}}