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Phagocytes play a critical role in the broad cancer immunoprevention efficacy of a novel agonist of CD137 pathway as a single agent 4286

Year: 2025
Type: article
Abstract: Description SA-4-1BBL as a single agent shows cancer immunoprevention efficacy against various tumor types. Inasmuch as naïve T cells do not constitutively express CD137, we herein tested the role of innate immune cells in the efficacy. C57BL/6 and BALB/c mice were treated s.c. twice 2 weeks apart with SA-4-1BBL followed by challenged with TC-1, LLC, or A20 tumor cells two weeks later. Phagocytes were depleted using clodronate-liposomes 2 days prior to each SA-4-1BBL treatment or 2 days before the tumor challenge. Since clodronate does not deplete neutrophils, anti-Ly6G Ab was administrated to a group of mice 2 days before each SA-4-1BBL treatment. Saline or PBS-liposome-treated mice served as controls. Deep immunophenotyping of dLN from mice tumor-free at 60 days post-challenge was performed to assess immune correlates. SA-4-1BBL prevented tumor growth in > 70% of mice. Deep immunophenotyping showed significantly increased absolute cell number of NK, NKT cells, macrophages, and neutrophils in SA-4-1BBL compared to naïve mice. Clodronate-mediated phagocyte depletion significantly reduced the efficacy, with only ∼20% of mice remaining tumor-free. Importantly, neutrophil depletion did not impact the cancer immunoprevention efficacy. These findings indicate that phagocytes are indispensable for the prophylactic, tumor-type independent immunoprevention efficacy of SA-4-1BBL. Identification of innate immune cells that exert cancer immunoprevention may have significant clinical implications. Funding Sources NIH UG3CA290305 Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)
DOI: 10.1093/jimmun/vkaf283.1986
Language: English
Subfield: Immunology
Open Access status: bronze
OpenAlex ID: W4416448262
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