{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T19:56:29Z","timestamp":1793476589306,"version":"4.5.0"},"reference-count":29,"publisher":"American Association for Cancer Research (AACR)","issue":"1","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Weak and ineffective antitumor cytotoxic T lymphocyte (CTL) responses can be rescued by immunomodulatory mAbs targeting PD-1 or CD137. Using Batf3\u2212\/\u2212 mice, which are defective for cross-presentation of cell-associated antigens, we show that BATF3-dependent dendritic cells (DC) are essential for the response to therapy with anti-CD137 or anti\u2013PD-1 mAbs. Batf3\u2212\/\u2212 mice failed to prime an endogenous CTL-mediated immune response toward tumor-associated antigens, including neoantigens. As a result, the immunomodulatory mAbs could not amplify any therapeutically functional immune response in these mice. Moreover, administration of systemic sFLT3L and local poly-ICLC enhanced DC-mediated cross-priming and synergized with anti\u2013CD137- and anti\u2013PD-1\u2013mediated immunostimulation in tumor therapy against B16-ovalbumin\u2013derived melanomas, whereas this function was lost in Batf3\u2212\/\u2212 mice. These experiments show that cross-priming of tumor antigens by FLT3L- and BATF3-dependent DCs is crucial to the efficacy of immunostimulatory mAbs and represents a very attractive point of intervention to enhance their clinical antitumor effects.<\/jats:p>\n                  <jats:p>Significance: Immunotherapy with immunostimulatory mAbs is currently achieving durable clinical responses in different types of cancer. We show that cross-priming of tumor antigens by BATF3-dependent DCs is a key limiting factor that can be exploited to enhance the antitumor efficacy of anti\u2013PD-1 and anti-CD137 immunostimulatory mAbs. Cancer Discov; 6(1); 71\u20139. \u00a92015 AACR.<\/jats:p>\n                  <jats:p>See related commentary by Robert-Tissot and Speiser, p. 17.<\/jats:p>\n                  <jats:p>This article is highlighted in the In This Issue feature, p. 1<\/jats:p>","DOI":"10.1158\/2159-8290.cd-15-0510","type":"journal-article","created":{"date-parts":[[2015,10,22]],"date-time":"2015-10-22T21:58:24Z","timestamp":1445551104000},"page":"71-79","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":486,"title":["Cancer Immunotherapy with Immunomodulatory Anti-CD137 and Anti\u2013PD-1 Monoclonal Antibodies Requires BATF3-Dependent Dendritic Cells"],"prefix":"10.1158","volume":"6","author":[{"given":"Alfonso R.","family":"S\u00e1nchez-Paulete","sequence":"first","affiliation":[{"name":"1Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, and Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdISNA), Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Cueto","sequence":"additional","affiliation":[{"name":"2Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain."},{"name":"3Department of Biochemistry, Faculty of Medicine, Universidad Aut\u00f3noma de Madrid, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Mart\u00ednez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"2Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Labiano","sequence":"additional","affiliation":[{"name":"1Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, and Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdISNA), Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aizea","family":"Morales-Kastresana","sequence":"additional","affiliation":[{"name":"1Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, and Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdISNA), Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda E.","family":"Rodr\u00edguez-Ruiz","sequence":"additional","affiliation":[{"name":"4University Clinic, University of Navarra and Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdISNA), Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Jure-Kunkel","sequence":"additional","affiliation":[{"name":"5Bristol-Myers Squibb, Princeton, New Jersey."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arantza","family":"Azpilikueta","sequence":"additional","affiliation":[{"name":"1Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, and Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdISNA), Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Angela","family":"Aznar","sequence":"additional","affiliation":[{"name":"1Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, and Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdISNA), Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 I.","family":"Quetglas","sequence":"additional","affiliation":[{"name":"1Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, and Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdISNA), Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sancho","sequence":"additional","affiliation":[{"name":"2Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Melero","sequence":"additional","affiliation":[{"name":"1Division of Immunology and 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