@article{QIAO2025, 
author = {CHENXIAO QIAO and YIPENG XU and YEDIE HE and ZHIJIAN CAI and HUA WANG},
title = {Oncolytic adenovirus H101 enhances the anti-tumor effects of PD-1 blockade via CD47 downregulation in tumor cells},
year = {2025},
journal = {Oncology Research},
volume = {33},
number = {5},
pages = {1161-1172},
keywords = {Cancer, Oncolytic adenovirus, Macrophage, CD47, Programmed cell death protein 1 blockade (PD-1 blockade)},
url = {https://www.sciopen.com/article/10.32604/or.2024.055746},
doi = {10.32604/or.2024.055746},
abstract = {ObjectiveTo investigate the anti-tumor effects of an E1B55KD-deleted oncolytic adenovirus, H101, in combination with a humanized anti-PD-1 (Programmed cell death protein 1) monoclonal antibody, Camrelizumab.MethodsAnti-tumor efficacy of intratumoral injection of H101 or/and intraperitoneal injection of Camrelizumab were evaluated in an immune system humanized NOD PrkdcscidIl2rg-/- mice subcutaneous (S.C.) tumor model, established with human glioblastoma of unknown origin cell line U87-MG, and human bladder cancer cell line T24 and YTS-1. The mechanism by which H101 induced anti-tumor immunity were also investigated.ResultsCombining H101 with Camrelizumab demonstrated more potent anti-tumor effects than monotherapy in mouse S.C. tumor model. Increased tumor-infiltrating T cells were observed in the combined treatment group. H101 infection decreased the expression of CD47 in cancer cells, thereby promoting macrophages to phagocytose cancer cells. Following the H101-mediated activation of macrophages, increased levels of cytokines, including TNF, IL-12 and IFN-γ were observed. Moreover, when induced THP-1 cells were co-cultured with H101-treated cancer cells, expression of IFN-γ was increased in T cells. Elimination of IL-12 using an anti-IL-12 antibody abolished IFN-γ production from T cells. In addition, infection with H101 increased PD-L1 expression in YTS-1 cells. These results suggested that H101 may act synergistically to enhance the therapeutic efficacy of PD-1 blockade in cancer via suppressing CD47 signaling, which may promote macrophages to phagocytose tumor cells and activate CD8+ T cells.ConclusionThe combination of H101 with PD-1 blockade exhibits potential as a novel strategy for the treatment of cancer.}
}