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T cells and cytokines play a critical role in tumour progression, but the T cell landscape correlated with HCC prognosis remains undepicted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The prognostic significance of intra\u2010tumoural immune cells, chemokines and cytokines were analysed using mass cytometry, bulk RNA sequencing and scRNA\u2010seq data with survival information. The signature of CD4\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      double positive T (DPT) cells was constructed using scRNA\u2010seq and quantified by ssGSEA scores, whose association with the response to atezolizumab plus bevacizumab was evaluated. Cellular cross\u2010talk and spatial patterns were analysed by scRNA\u2010seq and spatial transcriptomics. Flow cytometry, gene knockdown, transwell migration, co\u2010culture assays, qPCR and wound healing assay were performed to further validate the DPT\u2010associated niche.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      Higher intra\u2010tumoural levels of DPT cells, CD45RA\n                      <jats:sup>+<\/jats:sup>\n                      CD4\n                      <jats:sup>+<\/jats:sup>\n                      conventional T cells, HBEGF and CX3CR1 were associated with unfavourable prognosis in HCC. In contrast, higher infiltration of CD161\n                      <jats:sup>+<\/jats:sup>\n                      CD45RA\n                      <jats:sup>\u2212<\/jats:sup>\n                      CD4\n                      <jats:sup>+<\/jats:sup>\n                      conventional T cells and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells correlated with prolonged survival. CD45\n                      <jats:sup>+<\/jats:sup>\n                      EpCAM\n                      <jats:sup>+<\/jats:sup>\n                      and CD45\n                      <jats:sup>+<\/jats:sup>\n                      \u03b1\u2010SMA\n                      <jats:sup>+<\/jats:sup>\n                      cells were more frequent in short\u2010term survivors. DPT infiltration was identified across HCC multi\u2010cohorts and syngeneic mouse models. In patients receiving atezolizumab plus bevacizumab, responders exhibited higher DPT ssGSEA scores than non\u2010responders. Multi\u2010omics analyses indicated cross\u2010talk and spatial association of DPT cells with capillary\u2010associated endothelial cells, supporting a pro\u2010tumour niche. HBEGF was positively correlated with DPT cells and highly expressed in endothelial compartments. Endothelial\u2010derived HBEGF knockdown reduced DPT migration. Moreover, DPT co\u2010culture increased expression of signatures associated with immunosuppressive checkpoints, chemokine signalling, epithelial\u2013mesenchymal transition and stemness in Hep3B cells and promoted their migration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings depicted the prognostic immune landscape of HCC by identifying distinct T cell populations and molecular interactions. DPT cells emerged as a critical biomarker for poor prognosis, and the endothelial\u2010derived HBEGF\u2013DPT axis could represent a potential therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70708","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T06:46:36Z","timestamp":1780382796000},"source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010omics insights for deciphering prognosis\u2010related T cell subsets in hepatocellular carcinoma"],"prefix":"10.1002","volume":"16","author":[{"given":"Guangzu","family":"Cui","sequence":"first","affiliation":[{"name":"Department of Oncology Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"National Clinical Research Center for Geriatric Disease Xiangya Hospital Central South University  Changsha Hunan 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