{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:26:18Z","timestamp":1792700778499,"version":"4.5.0"},"reference-count":79,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"653","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,7,13]]},"abstract":"<jats:p>\n                    T cell\u2013directed cancer immunotherapy often fails to generate lasting tumor control. Harnessing additional effectors of the immune response against tumors may strengthen the clinical benefit of immunotherapies. Here, we demonstrate that therapeutic targeting of the interferon-\u03b3 (IFN-\u03b3)\u2013interleukin-12 (IL-12) pathway relies on the ability of a population of natural killer (NK) cells with tissue-resident traits to orchestrate an antitumor microenvironment. In particular, we used an engineered adenoviral platform as a tool for intratumoral IL-12 immunotherapy (AdV5\u2013IL-12) to generate adaptive antitumor immunity. Mechanistically, we demonstrate that AdV5\u2013IL-12 is capable of inducing the expression of CC-chemokine ligand 5 (CCL5) in CD49a\n                    <jats:sup>+<\/jats:sup>\n                    NK cells both in tumor mouse models and tumor specimens from patients with cancer. AdV5\u2013IL-12 imposed CCL5-induced type I conventional dendritic cell (cDC1) infiltration and thus increased DC-CD8 T cell interactions. A similar observation was made for other IFN-\u03b3\u2013inducing therapies such as Programmed cell death 1 (PD-1) blockade. Conversely, failure to respond to IL-12 and PD-1 blockade in tumor models with low CD49a\n                    <jats:sup>+<\/jats:sup>\n                    CXCR6\n                    <jats:sup>+<\/jats:sup>\n                    NK cell infiltration could be overcome by intratumoral delivery of CCL5. Thus, therapeutic efficacy depends on the abundance of NK cells with tissue-resident traits and, specifically, their capacity to produce the DC chemoattractant CCL5. Our findings reveal a barrier for T cell\u2013focused therapies and offer mechanistic insights into how T cell\u2013NK cell\u2013DC cross-talk can be enhanced to promote antitumor immunity and overcome resistance.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.abm9043","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T13:56:26Z","timestamp":1657720586000},"source":"Crossref","is-referenced-by-count":86,"title":["NK cells with tissue-resident traits shape response to immunotherapy by inducing adaptive antitumor immunity"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6043-5143","authenticated-orcid":true,"given":"Nicole","family":"Kirchhammer","sequence":"first","affiliation":[{"name":"Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital Basel, 4031 Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6755-7899","authenticated-orcid":true,"given":"Marcel P.","family":"Trefny","sequence":"additional","affiliation":[{"name":"Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital Basel, 4031 Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0270-0225","authenticated-orcid":true,"given":"Marina","family":"Natoli","sequence":"additional","affiliation":[{"name":"Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital Basel, 4031 Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3160-5542","authenticated-orcid":true,"given":"Dominik","family":"Br\u00fccher","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Zurich, 8057 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2162-7107","authenticated-orcid":true,"given":"Sheena N.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Zurich, 8057 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1502-2259","authenticated-orcid":true,"given":"Franziska","family":"Werner","sequence":"additional","affiliation":[{"name":"Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital Basel, 4031 Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9641-3720","authenticated-orcid":true,"given":"Victoria","family":"Koch","sequence":"additional","affiliation":[{"name":"Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital Basel, 4031 Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0324-2526","authenticated-orcid":true,"given":"David","family":"Schreiner","sequence":"additional","affiliation":[{"name":"Immune Cell Biology, Department of Biomedicine, University Hospital Basel, 4031 Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5153-9258","authenticated-orcid":true,"given":"Ewelina","family":"Bartoszek","sequence":"additional","affiliation":[{"name":"Microscopy Core Facility, Department of Biomedicine, University Hospital Basel, 4031 Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9958-9748","authenticated-orcid":true,"given":"M\u00e9lanie","family":"Buchi","sequence":"additional","affiliation":[{"name":"Cancer Immunology, Department of Biomedicine, University of Basel and University Hospital Basel, 4031 Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4533-371X","authenticated-orcid":true,"given":"Markus","family":"Schmid","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Zurich, 8057 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1670-2464","authenticated-orcid":true,"given":"Daniel","family":"Breu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Zurich, 8057 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5667-5128","authenticated-orcid":true,"given":"K. 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