{"entity": "researcher", "timestamp": "2026-09-28T12:19:00.849Z", "family": "Sallberg", "given": "Matti", "initials": "M", "orcid": "0000-0002-8858-5132", "affiliations": ["Division of Clinical Microbiology,Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden, Stockholm, Sweden.", "Karolinska ATMP center, Karolinska Institutet, Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/7ec0b37540734d0e9429f02d4898f188.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/7ec0b37540734d0e9429f02d4898f188"}}, "publications": [{"entity": "publication", "iuid": "c1d92c04a19b4e789c03a5cb3e222b2a", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c1d92c04a19b4e789c03a5cb3e222b2a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c1d92c04a19b4e789c03a5cb3e222b2a"}}, "title": "Unlocking novel T cell-based immunotherapy for hepatocellular carcinoma through neoantigen-driven T cell receptor isolation.", "authors": [{"family": "Maravelia", "given": "Panagiota", "initials": "P"}, {"family": "Yao", "given": "Haidong", "initials": "H", "orcid": "0009-0007-4791-5063", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/94e1e6cd558a4127b0f7ed9e62a1a927.json"}}, {"family": "Cai", "given": "Curtis", "initials": "C", "orcid": "0000-0002-3490-4361", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f178bae67ac7483890f6e4ae97c8a16b.json"}}, {"family": "Nascimento Silva", "given": "Daniela", "initials": "D", "orcid": "0000-0003-2165-4989", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a996395a23c24200abce9e6635bb8b68.json"}}, {"family": "Fransson", "given": "Jennifer", "initials": "J", "orcid": "0000-0003-4762-901X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f3840b7c31274f85b259ab28462bd546.json"}}, {"family": "Nilsson", "given": "Ola B", "initials": "OB", "orcid": "0000-0002-7516-1760", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/13f7501688f746b3bd46e9a5b662edea.json"}}, {"family": "Lu", "given": "Yong-Chen William", "initials": "YW", "orcid": "0000-0002-0275-9825", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/97d061ef86fb477184c0544fbdf29f9a.json"}}, {"family": "Micke", "given": "Patrick", "initials": "P", "orcid": "0000-0003-1210-5961", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b4b9d0f748440e19db93d4543bbe25f.json"}}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Gatto", "given": "Francesca", "initials": "F"}, {"family": "Rovesti", "given": "Giulia", "initials": "G", "orcid": "0000-0002-2761-9482", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/602ddd0aae27476b82d3a22601cee075.json"}}, {"family": "Carlsten", "given": "Mattias", "initials": "M", "orcid": "0000-0001-9815-0012", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dc3067626d864f66aeec08b79fef94dd.json"}}, {"family": "Sallberg", "given": "Matti", "initials": "M", "orcid": "0000-0002-8858-5132", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7ec0b37540734d0e9429f02d4898f188.json"}}, {"family": "St\u00e5l", "given": "Per", "initials": "P"}, {"family": "Jorns", "given": "Carl", "initials": "C", "orcid": "0000-0001-7727-8113", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ef68cb234b3141278a29a407ed988b32.json"}}, {"family": "Buggert", "given": "Marcus", "initials": "M", "orcid": "0000-0003-0633-1719", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cf1bb88eef764f8bb81bdd6d8a231113.json"}}, {"family": "Pasetto", "given": "Anna", "initials": "A", "orcid": "0000-0002-5254-2173", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c89f8e80b70a46c3bd0f8d34deba11ce.json"}}], "type": "journal article", "published": "2025-06-06", "journal": {"title": "Gut", "issn": "1468-3288", "volume": "74", "issue": "7", "pages": "1125-1136", "issn-l": "0017-5749"}, "abstract": "Tumour-infiltrating T cells can mediate both antitumour immunity and promote tumour progression by creating an immunosuppressive environment. This dual role is especially relevant in hepatocellular carcinoma (HCC), characterised by a unique microenvironment and limited success with current immunotherapy.\n\nWe evaluated T cell responses in patients with advanced HCC by analysing tumours, liver flushes and liver-draining lymph nodes, to understand whether reactive T cell populations could be identified despite the immunosuppressive environment.\n\nT cells isolated from clinical samples were tested for reactivity against predicted neoantigens. Single-cell RNA sequencing was employed to evaluate the transcriptomic and proteomic profiles of antigen-experienced T cells. Neoantigen-reactive T cells expressing 4-1BB were isolated and characterised through T-cell receptor (TCR)-sequencing.\n\nBioinformatic analysis identified 542 candidate neoantigens from seven patients. Of these, 78 neoantigens, along with 11 hotspot targets from HCC driver oncogenes, were selected for ex vivo T cell stimulation. Reactivity was confirmed in co-culture assays for 14 targets, with most reactive T cells derived from liver flushes and lymph nodes. Liver flush-derived T cells exhibited central memory and effector memory CD4+ with cytotoxic effector profiles. In contrast, tissue-resident memory CD4+ and CD8+ T cells with an exhausted profile were primarily identified in the draining lymph nodes.\n\nThese findings offer valuable insights into the functional profiles of neoantigen-reactive T cells within and surrounding the HCC microenvironment. T cells isolated from liver flushes and tumour-draining lymph nodes may serve as a promising source of reactive T cells and TCRs for further use in immunotherapy for HCC.", "doi": "10.1136/gutjnl-2024-334148", "pmid": "39832892", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12611799"}, {"db": "pii", "key": "gutjnl-2024-334148"}], "notes": [], "created": "2026-09-23T11:33:38.913Z", "modified": "2026-09-23T11:33:39.458Z"}]}