2026-04-18T17:18:21Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/161152025-06-18T06:35:27Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609col_20.500.12105_19616
Repisalud
author
Morales-Molina, Alvaro
author
Rodriguez-Milla, Miguel A
author
Gambera, Stefano
author
Cejalvo, Teresa
author
Andres, Belen de
author
Gaspar, Maria Luisa
author
Garcia-Castro, Javier
funder
Instituto de Salud Carlos III
funder
Comunidad de Madrid (España)
funder
Fundación Oncohematología Infantil
funder
Asociación Pablo Ugarte contra el cáncer infantil
funder
Asociación de Familias de Niños con Cáncer de Castilla-La Mancha
2023-05-24T08:28:52Z
2023-05-24T08:28:52Z
2023-03
Cancer Res Commun. 2023 Mar 1;3(3):347-360.
http://hdl.handle.net/20.500.12105/16115
36875156
10.1158/2767-9764.CRC-22-0365
2767-9764
Cancer research communications
Cancer immunotherapy aims to activate the immune system. Some immunotherapeutic agents can be loaded in carrier cells for delivering to the tumors. However, a challenge with cell-based therapies is the selection of the appropriate cells to produce effective clinical outcomes. We hypothesize that therapies based on cells presenting a natural low proinflammatory profile ("silent cells") in the peripheral blood would result in better antitumor responses by increasing their homing to the tumor site. We studied our hypothesis in an immunotherapy model consisting of mesenchymal stromal cells (MSCs) carrying oncolytic adenoviruses for the treatment of immunocompetent mice. Toll-like receptor signaling-deficient cells (TLR4, TLR9, or MyD88 knockout) were used as "silent cells," while regular MSCs were used as control. Although in vitro migration was similar in regular and knockout carrier cells, in vivo tumor homing of silent cells was significantly higher after systemic administration. This better homing to the tumor site was highly related to the mild immune response triggered by these silent cells in peripheral blood. As a result, the use of silent cells significantly improved the antitumor efficacy of the treatment in comparison with the use of regular MSCs. While cancer immunotherapies generally aim to boost local immune responses in the tumor microenvironment, low systemic inflammation after systemic administration of the treatment may indeed enhance their tumor homing and improve the overall antitumor effect. These findings highlight the importance of selecting appropriate donor cells as therapeutic carriers in cell-based therapies for cancer treatment. Cells carrying drugs, virus, or other antitumor agents are commonly used for the treatment of cancer. This research shows that silent cells are excellent carriers for immunotherapies, improving tumor homing and enhancing the antitumor effect.
eng
Toll-like Receptor Signaling-deficient Cells Enhance Antitumor Activity of Cell-based Immunotherapy by Increasing Tumor Homing
research article
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Toll-likeReceptorSignaling-deficientCells_2023.pdf
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Toll-likeReceptorSignaling-deficientCells_2023.pdf.txt