{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:50:17Z","timestamp":1792450217390,"version":"4.5.0"},"reference-count":236,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:00:00Z","timestamp":1620345600000},"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:p>\n                    Hepatocellular Carcinoma (HCC) is a highly prevalent malignancy that develops in patients with chronic liver diseases and dysregulated systemic and hepatic immunity. The tumor microenvironment (TME) contains tumor-associated macrophages (TAM), cancer-associated fibroblasts (CAF), regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) and is central to mediating immune evasion and resistance to therapy. The interplay between these cells types often leads to insufficient antigen presentation, preventing effective anti-tumor immune responses.\n                    <jats:italic>In situ<\/jats:italic>\n                    vaccines harness the tumor as the source of antigens and implement sequential immunomodulation to generate systemic and lasting antitumor immunity. Thus,\n                    <jats:italic>in situ<\/jats:italic>\n                    vaccines hold the promise to induce a switch from an immunosuppressive environment where HCC cells evade antigen presentation and suppress T cell responses towards an immunostimulatory environment enriched for activated cytotoxic cells. Pivotal steps of\n                    <jats:italic>in situ<\/jats:italic>\n                    vaccination include the induction of immunogenic cell death of tumor cells, a recruitment of antigen-presenting cells with a focus on dendritic cells, their loading and maturation and a subsequent cross-priming of CD8+ T cells to ensure cytotoxic activity against tumor cells. Several\n                    <jats:italic>in situ<\/jats:italic>\n                    vaccine approaches have been suggested, with vaccine regimens including oncolytic viruses, Flt3L, GM-CSF and TLR agonists. Moreover, combinations with checkpoint inhibitors have been suggested in HCC and other tumor entities. This review will give an overview of various\n                    <jats:italic>in situ<\/jats:italic>\n                    vaccine strategies for HCC, highlighting the potentials and pitfalls of\n                    <jats:italic>in situ<\/jats:italic>\n                    vaccines to treat liver cancer.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.650486","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:42:16Z","timestamp":1620348136000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":62,"title":["In Situ Vaccination as a Strategy to Modulate the Immune Microenvironment of Hepatocellular 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