{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T01:57:19Z","timestamp":1777773439203,"version":"3.51.4"},"posted":{"date-parts":[[2025,8,25]]},"group-title":"Immunology","reference-count":60,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Adoptive Cell Therapy (ACT) has achieved curative responses in hematological malignancies, yet its translation to solid tumors remains limited by manufacturing bottlenecks, systemic toxicities, and poor T-cell infiltration and persistence within the immunosuppressive tumor microenvironment (TME). Here, we report the development and mechanism of ACTIVATE (Adoptive Cell Therapy and Immunostimulatory Vehicle for Anti-Tumor Efficacy), which leverages an injectable hydrogel depot technology that forms a transient inflammatory niche for localized co-delivery of adoptive T cells and native cytokines. By tuning cytokine identity, ACTIVATE enables precise modulation of T-cell expansion, effector function, and interaction with endogenous immune networks. We found that enhancing T-cell proliferation alone is insufficient to drive robust tumor control; instead, coordinated engagement of both adoptive and endogenous immune responses is critical for durable anti-tumor efficacy.\n                  <jats:italic>In vivo<\/jats:italic>\n                  , this orchestration via ACTIVATE led to enhanced infiltration and cytotoxicity of both adoptive and host-derived immune effectors, while driving robust recruitment and activation of T cells, B cells, dendritic cells, and macrophages in the tumor-draining lymph nodes. This local immune activation can further reshape the TME, promoting antigen presentation and suppressing immunoregulatory populations, thus enhancing anti-tumor efficacy in murine melanoma and lymphoma models. These findings establish ACTIVATE as a modular platform for orchestrating coordinated immune responses to improve ACT outcomes in solid tumors.\n                <\/jats:p>","DOI":"10.1101\/2025.08.22.671875","type":"posted-content","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T16:40:13Z","timestamp":1756140013000},"source":"Crossref","is-referenced-by-count":1,"title":["A Transient Immunostimulatory Niche Synergizes Adoptive and Endogenous Immunity for Enhanced Tumor Control"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6242-2506","authenticated-orcid":false,"given":"Anahita","family":"Nejatfard","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Stanford University, Stanford, CA, 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9285-1018","authenticated-orcid":false,"given":"John H.","family":"Klich","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4183-0153","authenticated-orcid":false,"given":"Noah","family":"Eckman","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Stanford University, Stanford, CA, 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6477-8936","authenticated-orcid":false,"given":"Sophia J.","family":"Bailey","sequence":"additional","affiliation":[{"name":"Department of Materials Science & Engineering, Stanford University, Stanford, CA, 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3340-4410","authenticated-orcid":false,"given":"Kyra","family":"Gillard","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Stanford University, Stanford, CA, 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel Ramos","family":"Mejia","sequence":"additional","affiliation":[{"name":"Department of Materials Science & Engineering, Stanford University, Stanford, CA, 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0539-5166","authenticated-orcid":false,"given":"Ben S.","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8278-1354","authenticated-orcid":false,"given":"Jerry","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9961-7673","authenticated-orcid":false,"given":"John W.","family":"Hickey","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2301-7126","authenticated-orcid":false,"given":"Eric A.","family":"Appel","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA"},{"name":"Department of Materials Science & Engineering, Stanford University, Stanford, CA, 94305, USA"},{"name":"Sarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA"},{"name":"Wood Institute for the Environment, Stanford University, Stanford, CA, 94305, USA"},{"name":"Department of Pediatrics (Endocrinology), Stanford University, Stanford, CA, 94305, 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