Data from Depletion of Conventional Type-1 Dendritic Cells in Established Tumors Suppresses Immunotherapy Efficacy

• DOI: 10.1158/0008-5472.c.6514338.v1
• Publication Date: 2023-03-31T20:52:03Z
• Authors: Alvaro Teijeira; Saray Garasa; Carlos Luri-Rey; Carlos de Andrea; Maria Gato; Carmen Molina; Tsuneyasu Kaisho; Assunta Cirella; Arantza Azpilikueta; Steffanie K. Wculek; Josune Egea; Irene Olivera; Inmaculada Rodriguez; Ana Rouzaut; Vladislav Verkhusha; Karmele Valencia; David Sancho; Pedro Berraondo; Ignacio Melero
• Keywords: CD137; Diphtheria Toxin; Cancer Immunotherapy

<div>Abstract<p>The ability of conventional type-1 dendritic cells (cDC1) to cross-present tumor antigens CD8<sup>+</sup> T is critical for the induction antitumor CTLs. Mice that are constitutively deficient in cDC1 have been reported fail respond immunotherapy strategies based on checkpoint inhibitors. However, further work needed clarify precise time during treatment required beneficial effect treatment. Here, we used a refined XCR1-DTR-Venus transgenic mouse model acutely deplete and trace their behavior using intravital microscopy. Diphtheria toxin–mediated depletion prior with anti–PD-1 and/or anti-CD137 immunostimulatory mAbs completely ablated efficacy. The efficacy adoptive T-cell therapy was also hampered by depletion. After onset treatment, cDC1s only moderately reduced therapeutic mAbs. Intravital microscopy liver-engrafted tumors revealed changes intratumoral mice receiving immunotherapy, diphtheria toxin impaired infiltration function. These results reveal functional integrity compartment at various immunotherapies successfully treat established tumors.</p>Significance:<p>These findings models demonstrate regimens precluded elimination these cells.</p></div>