2026-07-23T17:11:30Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/97212024-09-27T09:14:28Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Sánchez-Paulete, Alfonso R
author
Cueto, Francisco J.
author
Martínez-López, María
author
Labiano, Sara
author
Morales-Kastresana, Aizea
author
Rodríguez-Ruiz, María E
author
Jure-Kunkel, Maria
author
Azpilikueta, Arantza
author
Aznar, M Angela
author
Quetglas, José I
author
Sancho, David
author
Melero, Ignacio
funder
Ministerio de Ciencia e Innovación (España)
funder
Gobierno de Navarra (España)
funder
Unión Europea. Comisión Europea
funder
Ministerio de Economía y Competitividad (España)
funder
Fundación ProCNIC
2020-04-23T13:36:42Z
2020-04-23T13:36:42Z
2016-01
Cancer Discov. 2016; 6(1):71-9
10.1158/2159-8290.CD-15-0510
2159-8290
2159-8274
Cancer discovery
26493961
http://hdl.handle.net/20.500.12105/9721
UNLABELLED: Weak and ineffective antitumor cytotoxic T lymphocyte (CTL) responses can be rescued by immunomodulatory mAbs targeting PD-1 or CD137. Using Batf3(-/-) 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-PD-1 mAbs. Batf3(-/-) 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-CD137- and anti-PD-1-mediated immunostimulation in tumor therapy against B16-ovalbumin-derived melanomas, whereas this function was lost in Batf3(-/-) 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. 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-PD-1 and anti-CD137 immunostimulatory mAbs.
eng
Cancer Immunotherapy with Immunomodulatory Anti-CD137 and Anti-PD-1 Monoclonal Antibodies Requires BATF3-Dependent Dendritic Cells
journal article
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