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oai:recercat.cat:20.500.12327/30092025-10-22T11:32:00Zcom_2072_4428com_2072_4427col_2072_487898

Anti-PD-L1 Immunotherapy of Chronic Virus Infection Improves Virus Control without Augmenting Tissue Damage by Fibrosis Casella, Valentina Cebollada Rica, Paula Argilaguet, Jordi Vidal, Enric González-Cao, María Güerri-Fernandez, Roberto Bocharov, Gennady Meyerhans, Andreas Producció Animal Sanitat Animal 619 Immunotherapy with checkpoint inhibitors, albeit commonly used against tumors, is still at its infancy against chronic virus infections. It relies on the reinvigoration of exhausted T lymphocytes to eliminate virus-infected cells. Since T cell exhaustion is a physiological process to reduce immunopathology, the reinvigoration of these cells might be associated with an augmentation of pathological changes. To test this possibility, we here analyzed in the model system of chronic lymphocytic choriomeningitis virus (LCMV)-infected mice whether treatment with the checkpoint inhibitor anti-PD-L1 antibody would increase CD8 T cell-dependent fibrosis. We show that preexisting spleen fibrosis did not worsen under conditions that increase CD8 T cell functionality and reduce virus loads suggesting that the CD8 T cell functionality increase remained below its pathogenicity threshold. These promising findings should further encourage immunotherapeutic trials against chronic virus infections. This work was supported by grants PID2022-141395OB-I00 funded by MICIU/AEI/10.13039/ 501100011033 and by ERDF/EU A way of making Europe, HR17-00199 from the “la Caixa” Foundation and the Russian Science Foundation grant No. 23-11-00116. info:eu-repo/semantics/publishedVersion 2024-05-17 info:eu-repo/semantics/article Casella, Valentina, Paula Cebollada Rica, Jordi Argilaguet, Enric Vidal, María González-Cao, Roberto Güerri-Fernandez, Gennady Bocharov, and Andreas Meyerhans. 2024. “Anti-PD-L1 Immunotherapy of Chronic Virus Infection Improves Virus Control Without Augmenting Tissue Damage by Fibrosis.” Viruses 16 (5): 799. doi:10.3390/v16050799 1999-4915 http://hdl.handle.net/20.500.12327/3009 https://doi.org/10.3390/v16050799 eng Viruses MICINN/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I/PID2022-141395OB-I00/ES/COORDINACION Y COOPERACION DE CELULAS INMUNES DURANTE INFECCIONES VIRALES AGUDAS Y CRONICAS/ FEDER/ / /EU/ / Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess 9 MDPI