{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T06:02:39Z","timestamp":1784872959054,"version":"3.55.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"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>Background<\/jats:title>\n                    <jats:p>Identifying upstream molecular regulators linking tumor proliferation with immune-related alterations remains an important challenge in cancer therapy. NTMT1 (METTL11A), a protein N-terminal methyltransferase, has been implicated in tumorigenesis; however, its role in coordinating tumor\u2013immune interaction is poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed integrative single-cell RNA sequencing (GSE208653) and spatial transcriptomics (GSE208654) analyses to characterize NTMT1 expression and function in cervical cancer. Spatial deconvolution and microenvironmental co-localization analyses were used to define context-specific effects. Functional validation was conducted using RT\u2013qPCR, Western blotting, multiplex immunofluorescence, and flow cytometry-based assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NTMT1 exhibited heterogeneous expression across epithelial and immune cell populations, with enrichment in squamous cell carcinoma. Spatial transcriptomics revealed that NTMT1-positive regions were associated with altered immune composition, including reduced macrophage and increased NK\/T cell infiltration. In epithelial-enriched regions, NTMT1 expression correlated with activation of cell cycle pathways, including MYC, E2F1, CDK1, and CCNB1. Functional experiments demonstrated that NTMT1 promotes cell cycle progression via MYC upregulation. In epithelial\u2013NK\/T co-localization niches, NTMT1 was associated with modulation of antigen presentation pathways and suppression of HLA-A expression. Functionally, NTMT1 overexpression reduced IFN-\u03b3 production by CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells under the co-culture conditions used in this study, which was partially restored by HLA-A re-expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      NTMT1 was identified as a candidate regulator associated with MYC activation and HLA-A suppression. Although the precise molecular mechanism remains to be elucidated, functional experiments demonstrated that NTMT1 overexpression was accompanied by increased MYC expression, reduced HLA-A expression, enhanced cell-cycle progression, and impaired CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell function. These findings identify NTMT1 as a candidate regulatory node associated with MYC activation and downstream HLA-A suppression, warranting further mechanistic and\n                      <jats:italic>in-vivo<\/jats:italic>\n                      investigation, highlighting NTMT1 as a promising candidate for future therapeutic investigation. Further\n                      <jats:italic>in vivo<\/jats:italic>\n                      studies will be required to determine its suitability as a target for combination immunotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1853434","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:34:55Z","timestamp":1784871295000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["NTMT1 (METTL11A) promotes MYC-dependent proliferation and downstream HLA-A suppression in cervical cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Jinling","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gynecology, Shenzhen People\u2019s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medical Sciences, Southern Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huibin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Shenzhen People\u2019s Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University)","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Shenzhen People\u2019s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)","place":["Shenzhen, 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