2026-04-29T04:08:30Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/150962024-09-27T09:59:36Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Teijeira, Alvaro author Garasa, Saray author Luri-Rey, Carlos author de Andrea, Carlos author Gato, Maria author Molina, Carmen author Kaisho, Tsuneyasu author Cirella, Assunta author Azpilikueta, Arantza author Wculek, Stefanie K author Egea, Josune author Olivera, Irene author Rodriguez, Inmaculada author Rouzaut, Ana author Verkhusha, Vladislav author Valencia, Karmele author Sancho, David author Berraondo, Pedro author Melero, Ignacio author 2022-09-21 The ability of conventional type-1 dendritic cells (cDC1) to cross-present tumor antigens to CD8+ T cells is critical for the induction of antitumor cytotoxic T lymphocytes. Mice that are constitutively deficient in cDC1 cells have been reported to fail to respond to immunotherapy strategies based on checkpoint inhibitors. However, further work is needed to clarify the precise time during immunotherapy treatment that cDC1 cells are required for the beneficial effect of treatment. Here, we used a refined XCR1-DTR-Venus transgenic mouse model to acutely deplete cDC1 cells and trace their behavior using intravital microscopy. Diphtheria toxin-mediated cDC1 depletion prior to immunotherapy treatment with anti-PD-1 and/or anti-CD137 immunostimulatory monoclonal antibodies (mAbs) completely ablated anti-tumor efficacy. The efficacy of adoptive T-cell therapy was also hampered by prior cDC1 depletion. After the onset of immunotherapy treatment, depletion of cDC1s only moderately reduced the therapeutic efficacy of anti-PD-1 and anti-CD137 mAbs. Intravital microscopy of liver-engrafted tumors revealed changes in the intratumoral behavior of cDC1 cells in mice receiving immunotherapy, and treatment with diphtheria toxin to deplete cDC1s impaired tumor T-cell infiltration and function. These results reveal that the functional integrity of the cDC1 compartment is required at the onset of various immunotherapies to successfully treat established tumors. Cancer Res . 2022 Sep 21;CAN-22-1046 http://hdl.handle.net/20.500.12105/15096 36130020 10.1158/0008-5472.CAN-22-1046 1538-7445 Cancer research Depletion of conventional type-1 dendritic cells in established tumors suppresses immunotherapy efficacy.