Cancer immunotherapy with immunomodulatory anti-CD137 and anti-PD-1 monoclonal antibodies requires Batf3-dependent dendritic cells
Palabras clave : 
Cancer immunotherapy
Immunomodulatory
Anti-PD-1 and anti-CD137
Dentritic cells
Fecha de publicación: 
2016
Editorial : 
American Association for Cancer Research
ISSN: 
2159-8274
Cita: 
Sánchez-Paulete AR, Cueto FJ, Martínez-López M, Labiano S, Morales-Kastresana A, Rodríguez-Ruiz ME, et al. Cancer immunotherapy with immunomodulatory anti-CD137 and anti-PD-1 monoclonal antibodies requires BATF3-dependent dendritic cells. Cancer Discov. 2016 Jan;6(1):71-79
Resumen
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.

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