Pub Date : 2026-03-03DOI: 10.1007/s00018-026-06121-4
Yue Zhang, Yan Gao, Xin Guan, Erfei Wang, Rui Tong
Cervical cancer (CC) is the most common gynecological malignancy and is strongly linked to human papillomavirus (HPV) infection. Currently, immune checkpoint blockade therapy has shown limited clinical benefits for CC, highlighting the need to find more effective therapeutic targets. LILRB4, a member of the leukocyte immunoglobulin-like receptor superfamily, is considered a key mediator of cancer immunosuppression. However, its role in the CC immune microenvironment remains unclear. Here, LILRB4 expression was upregulated in CC tissues, and high expression levels were positively associated with advanced disease and immunosuppressive genes in tumors. In an immunocompetent mouse model, LILRB4 expression in CC tumors increased with tumor growth, whereas blocking LILRB4 reduced tumor growth. Flow cytometry analysis revealed that blockade of LILRB4 reduced CD8+ T-cell exhaustion within tumors. Additionally, blockade of LILRB4 decreased the number of tumor‑infiltrating myeloid cells (TIMs), including myeloid‑derived suppressor cells (MDSCs) and M2 tumor‑associated macrophages (M2‑TAMs). Cell coculture experiments demonstrated that blockade of LILRB4 prevented CD8+ T-cell exhaustion by reducing the numbers of MDSCs and TAMs. Furthermore, HPV16 upregulated ApoE expression through transcriptional regulation, and LILRB4 mediated the suppression of CD8+ T cells by ApoE. Overall, the HPV16/ApoE/LILRB4 axis induced TIM-mediated suppression of CD8+ T cells, creating an immunosuppressive microenvironment that promoted CC progression.
{"title":"LILRB4 shapes an immunosuppressive microenvironment to drive cervical cancer progression through tumor-infiltrating myeloid cell expansion and CD8<sup>+</sup> T-cell suppression.","authors":"Yue Zhang, Yan Gao, Xin Guan, Erfei Wang, Rui Tong","doi":"10.1007/s00018-026-06121-4","DOIUrl":"10.1007/s00018-026-06121-4","url":null,"abstract":"<p><p>Cervical cancer (CC) is the most common gynecological malignancy and is strongly linked to human papillomavirus (HPV) infection. Currently, immune checkpoint blockade therapy has shown limited clinical benefits for CC, highlighting the need to find more effective therapeutic targets. LILRB4, a member of the leukocyte immunoglobulin-like receptor superfamily, is considered a key mediator of cancer immunosuppression. However, its role in the CC immune microenvironment remains unclear. Here, LILRB4 expression was upregulated in CC tissues, and high expression levels were positively associated with advanced disease and immunosuppressive genes in tumors. In an immunocompetent mouse model, LILRB4 expression in CC tumors increased with tumor growth, whereas blocking LILRB4 reduced tumor growth. Flow cytometry analysis revealed that blockade of LILRB4 reduced CD8<sup>+</sup> T-cell exhaustion within tumors. Additionally, blockade of LILRB4 decreased the number of tumor‑infiltrating myeloid cells (TIMs), including myeloid‑derived suppressor cells (MDSCs) and M2 tumor‑associated macrophages (M2‑TAMs). Cell coculture experiments demonstrated that blockade of LILRB4 prevented CD8<sup>+</sup> T-cell exhaustion by reducing the numbers of MDSCs and TAMs. Furthermore, HPV16 upregulated ApoE expression through transcriptional regulation, and LILRB4 mediated the suppression of CD8<sup>+</sup> T cells by ApoE. Overall, the HPV16/ApoE/LILRB4 axis induced TIM-mediated suppression of CD8<sup>+</sup> T cells, creating an immunosuppressive microenvironment that promoted CC progression.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12979764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01DOI: 10.1007/s00018-026-06103-6
Fia B Larsen, Birthe B Kragelund, Kresten Lindorff-Larsen, Pétur O Heidarsson, Rasmus Hartmann-Petersen
{"title":"Proteasomal control of transcription factors: mechanisms, regulation and dysregulation.","authors":"Fia B Larsen, Birthe B Kragelund, Kresten Lindorff-Larsen, Pétur O Heidarsson, Rasmus Hartmann-Petersen","doi":"10.1007/s00018-026-06103-6","DOIUrl":"10.1007/s00018-026-06103-6","url":null,"abstract":"","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12979741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-28DOI: 10.1007/s00018-026-06119-y
Clara Llorente-González, Kamila Mustafina, Gloria Asensio-Juárez, Marina Garrido-Casado, Vanessa C Talayero, Rafael Pérez-Díaz, Hugo Ramos-Solano, James R Sellers, Krishna Chinthalapudi, Paul W Wiseman, Sarah M Heissler, Miguel Vicente-Manzanares
{"title":"MYH9 mutations differentially stabilize non-muscle myosin II filaments and induce distinct cellular aggregation phenotypes.","authors":"Clara Llorente-González, Kamila Mustafina, Gloria Asensio-Juárez, Marina Garrido-Casado, Vanessa C Talayero, Rafael Pérez-Díaz, Hugo Ramos-Solano, James R Sellers, Krishna Chinthalapudi, Paul W Wiseman, Sarah M Heissler, Miguel Vicente-Manzanares","doi":"10.1007/s00018-026-06119-y","DOIUrl":"10.1007/s00018-026-06119-y","url":null,"abstract":"","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-27DOI: 10.1007/s00018-025-06069-x
Wen Hu, Xiao-Yi Wang, Xiao-Jun Zhan, Pei Pei, Ya-Ru Kong, Jie Ji, Jia Liu, Shan Wang, Jun Tai
{"title":"Mettl3-mediated m6A disruption of olfactory bulb glutamatergic metabolism homeostasis via the Wnt pathway in aging leads to olfactory dysfunction.","authors":"Wen Hu, Xiao-Yi Wang, Xiao-Jun Zhan, Pei Pei, Ya-Ru Kong, Jie Ji, Jia Liu, Shan Wang, Jun Tai","doi":"10.1007/s00018-025-06069-x","DOIUrl":"10.1007/s00018-025-06069-x","url":null,"abstract":"","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-26DOI: 10.1007/s00018-026-06107-2
Chiara Maria Calvanese, Vincenzo Valentino, Annachiara De Prisco, Serena Allesina, Angela Amoruso, Francesca Deidda, Annalisa Visciglia, Danilo Ercolini, Marco Pane, Francesca De Filippis
{"title":"Women's health is a team effort: probiogenomics supports the development of a multi-species vaginal probiotic.","authors":"Chiara Maria Calvanese, Vincenzo Valentino, Annachiara De Prisco, Serena Allesina, Angela Amoruso, Francesca Deidda, Annalisa Visciglia, Danilo Ercolini, Marco Pane, Francesca De Filippis","doi":"10.1007/s00018-026-06107-2","DOIUrl":"10.1007/s00018-026-06107-2","url":null,"abstract":"","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147288927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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