{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:10:09Z","timestamp":1785409809054,"version":"3.56.0"},"reference-count":95,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002737","name":"Regione Siciliana","doi-asserted-by":"publisher","award":["OBIND N.086202000366"],"award-info":[{"award-number":["OBIND N.086202000366"]}],"id":[{"id":"10.13039\/501100002737","id-type":"DOI","asserted-by":"publisher"}]},{"award":["OBIND N.086202000366"],"award-info":[{"award-number":["OBIND N.086202000366"]}],"id":[{"id":"https:\/\/ror.org\/025079t78","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Alpha-enolase (ENO1) is a multifunctional protein frequently overexpressed in solid tumors, where elevated levels are associated with aggressive behavior and poor prognosis. Beyond its canonical glycolytic role, ENO1 participates in immunoregulatory processes through distinct subcellular pools. Intracellular ENO1 shapes tumor-associated metabolic programs, while surface-exposed ENO1 functions as a plasminogen receptor and can engage innate immune signaling pathways. Post-translational modifications\u2014particularly citrullination and phosphorylation\u2014generate structurally altered epitopes that expand ENO1 antigenicity and enable adaptive immune recognition, including coordinated humoral and T-cell responses in cancer patients. These determinants of ENO1 immunogenicity have downstream consequences within the tumor microenvironment: immune-accessible ENO1 modulates myeloid cell recruitment, dendritic cell maturation, and macrophage polarization, while ENO1-dependent metabolic and signaling programs contribute to immune suppression and escape through multiple interconnected axes. Together, these mechanisms position ENO1 at the interface between tumor metabolism and immune regulation. Preclinical evidence demonstrates that ENO1-directed strategies\u2014including antibody-based targeting, DNA vaccination, and vaccines incorporating post-translationally modified ENO1 peptides\u2014can generate productive antitumor immunity and synergize with checkpoint blockade, supporting the rationale for ENO1 as an immunotherapeutic target. This review synthesizes current evidence within an integrated framework linking ENO1 dysregulation to its immunological consequences in cancer and discusses translational implications for ENO1-centered immunotherapy and immunoprevention.<\/jats:p>","DOI":"10.3390\/biom16071050","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:47:32Z","timestamp":1784508452000},"page":"1050","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ENO1 as an Immunoregulatory Hub in Cancer: Mechanisms and Translational Implications"],"prefix":"10.3390","volume":"16","author":[{"given":"Giovanni","family":"Perconti","sequence":"first","affiliation":[{"name":"Institute of Translational Pharmacology (IFT), National Research Council (CNR), Via Ugo La Malfa 153, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Bonura","sequence":"additional","affiliation":[{"name":"Institute of Translational Pharmacology (IFT), National Research Council (CNR), Via Ugo La Malfa 153, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Rubino","sequence":"additional","affiliation":[{"name":"Institute of Translational Pharmacology (IFT), National Research Council (CNR), Via Ugo La Malfa 153, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Giallongo","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research and Innovation (IRIB), National Research Council (CNR), Via Ugo La Malfa 153, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1186\/s12967-024-05847-8","article-title":"Role of ENO1 and its targeted therapy in tumors","volume":"22","author":"Li","year":"2024","journal-title":"J. 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