{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:15:44Z","timestamp":1792610144055,"version":"4.5.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T00:00:00Z","timestamp":1692057600000},"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>As an immune adjuvant, proinflammatory allogeneic dendritic cells (AlloDCs) have demonstrated promising immune-priming effects in several preclinical and clinical studies. The effector cells, including NK cells and T cells are widely acknowledged as pivotal factors in the effectiveness of cancer immunotherapy due to their ability to selectively identify and eradicate malignant cells. 4-1BB, as a costimulatory receptor, plays a significant role in the stimulation of effector cell activation. This study evaluated the anti-tumor effects when combining intratumoral administration of the immune-adjuvant AlloDCs with systemic \u03b14-1BB treatment directly acting on effector cells. In both the CT-26 murine colon carcinoma model and B16 murine melanoma model, AlloDCs demonstrated a significant enhancement in the therapeutic efficacy of \u03b14-1BB antibody. This enhancement was observed through the delayed growth of tumors and prolonged survival. Analysis of the tumor microenvironment (TME) in the combined-treatment group revealed an immune-inflamed TME characterized by increased infiltration of activated endogenous DCs and IFN\u03b3<jats:sup>+<\/jats:sup> CD8<jats:sup>+<\/jats:sup> T cells, showing reduced signs of exhaustion. Furthermore, there was an augmented presence of tissue-resident memory (T<jats:sub>RM<\/jats:sub>) CD8<jats:sup>+<\/jats:sup> T cells (CD103<jats:sup>+<\/jats:sup>CD49a<jats:sup>+<\/jats:sup>CD69<jats:sup>+<\/jats:sup>). The combination treatment also led to increased infiltration of CD39<jats:sup>+<\/jats:sup>CD103<jats:sup>+<\/jats:sup> tumor-specific CD8<jats:sup>+<\/jats:sup> T cells and neoantigen-specific T cells into the tumor. Additionally, the combined treatment resulted in a less immunosuppressive TME, indicated by decreased infiltration of myeloid-derived suppressor cells and Tregs. These findings suggest that the combination of intratumoral AlloDCs administration with systemic agonistic \u03b14-1BB treatment can generate a synergistic anti-tumor response, thereby warranting further investigation through clinical studies.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1146413","type":"journal-article","created":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T04:36:46Z","timestamp":1692247006000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Proinflammatory allogeneic dendritic cells enhance the therapeutic efficacy of systemic anti-4-1BB treatment"],"prefix":"10.3389","volume":"14","author":[{"given":"Arwa","family":"Ali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros","family":"Iskantar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Karlsson-Parra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2017.1397250","article-title":"Cancer vaccine based on a combination of an infection-enhanced adenoviral vector and pro-inflammatory allogeneic DCs leads to sustained antigen-specific immune responses in three melanoma models","volume":"7","author":"Fotaki","year":"2018","journal-title":"Oncoimmunology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2017.1395126","article-title":"Pro-inflammatory allogeneic DCs promote activation of bystander immune cells and thereby license antigen-specific T-cell responses","volume":"7","author":"Fotaki","year":"2018","journal-title":"Oncoimmunology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00019","article-title":"Phase 1 trial with the cell-based immune primer ilixadencel, alone, and combined with sorafenib, in advanced hepatocellular carcinoma","volume":"9","author":"Rizell","year":"2019","journal-title":"Front Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-020-02625-5","article-title":"Phase I trial evaluating safety and efficacy of intratumorally administered inflammatory allogeneic dendritic cells (ilixadencel) in advanced gastrointestinal stromal tumors","volume":"69","author":"Frobom","year":"2020","journal-title":"Cancer Immunol Immunother"},{"key":"B5","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1007\/s11095-018-2438-x","article-title":"Ilixadencel - 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