Histone deacetylase inhibitor and PD‑1 blockade synergistically inhibit B‑cell lymphoma progression in mice model by promoting T‑cell infiltration and apoptosis

  • Authors:
    • Tong Wang
    • Xu Ye
    • Hao Jiang
    • Yu Gao
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  • Published online on: August 7, 2024     https://doi.org/10.3892/or.2024.8792
  • Article Number: 133
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Abstract

B‑cell lymphoma is difficult to cure because of its biological and clinical heterogeneity, and due to native chemoresistance. Immunotherapies that overcome cancer‑induced immune evasion have been the center of recent developments in oncology. This is emphasized by the accomplishment of various agents that disrupt programmed cell death protein 1 (PD‑1)‑mediated immune suppression in diverse tumors. However, while PD‑1 blockade has been effective in numerous malignancies, a significant proportion of cancers, including B‑cell lymphoma, show certain rates of primary resistance to these therapeutic strategies. Histone deacetylase inhibitors (HDACis) have exhibited anticancer activity though suppressing cell proliferation, inducing differentiation and triggering apoptosis. The present study aimed to explore a therapeutic strategy combining a HDACi (romidepsin) and PD‑1 blockade (BMS‑1) in B‑cell lymphoma, utilizing a constructed mouse model of B‑cell lymphoma. The IC50 of the two inhibitors was confirmed by MTT assay, and their inhibitory effects were revealed to be dose‑ and time‑dependent. The data demonstrated that the combined treatment of romidepsin and BMS‑1 synergistically inhibited the growth of B‑cell lymphoma. Furthermore, it was revealed that romidepsin and BMS‑1 synergistically triggered apoptosis in mouse B‑cell lymphoma. The synergistic effect of these agents was capable of activating tumor‑infiltrating lymphocytes, particularly CD3+CD4+ and CD3+CD8+ T cells. The results of the present study underscore the potential of HDAC inhibition in conjunction with PD‑1 blockade as a novel therapeutic approach for B‑cell lymphoma, highlighting the synergistic effects of these two mechanisms in enhancing antitumor immunity.
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October-2024
Volume 52 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Wang T, Ye X, Jiang H and Gao Y: Histone deacetylase inhibitor and PD‑1 blockade synergistically inhibit B‑cell lymphoma progression in mice model by promoting T‑cell infiltration and apoptosis. Oncol Rep 52: 133, 2024.
APA
Wang, T., Ye, X., Jiang, H., & Gao, Y. (2024). Histone deacetylase inhibitor and PD‑1 blockade synergistically inhibit B‑cell lymphoma progression in mice model by promoting T‑cell infiltration and apoptosis. Oncology Reports, 52, 133. https://doi.org/10.3892/or.2024.8792
MLA
Wang, T., Ye, X., Jiang, H., Gao, Y."Histone deacetylase inhibitor and PD‑1 blockade synergistically inhibit B‑cell lymphoma progression in mice model by promoting T‑cell infiltration and apoptosis". Oncology Reports 52.4 (2024): 133.
Chicago
Wang, T., Ye, X., Jiang, H., Gao, Y."Histone deacetylase inhibitor and PD‑1 blockade synergistically inhibit B‑cell lymphoma progression in mice model by promoting T‑cell infiltration and apoptosis". Oncology Reports 52, no. 4 (2024): 133. https://doi.org/10.3892/or.2024.8792