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Natural killer (NK) cells are innate immune cells that are crucial for anticancer activity and have been developed as an immune cell therapy for leukemia. However, their limited effectiveness against solid tumors has prompted research into methods to enhance NK cell activity through combination therapies. Health supplements capable of boosting immune surveillance against tumor cells are gaining attention owing to their potential benefits. Resveratrol, a stilbenoid produced by several plants including peanuts and grapes, reportedly exerts anticancer effects and can activate immune cells. The peanut sprout extract cultivated with fermented sawdust medium (PSEFS) is rich in resveratrol, leveraging its health benefits in terms of the dry weight of herbal products, thus maximizing the utilization of resveratrol’s beneficial properties. Our study compared the efficacy of resveratrol and PSEFS and revealed that PSEFS significantly enhanced NK cell activation compared with an equivalent dose of resveratrol. We investigated the ability of PSEFS to potentiate NK cell anticancer activity, focusing on NK cell survival, tumor cell lysis, and NK cell activation in PSEFS-administered mice. Our findings suggest that PSEFS could be a potential NK cell booster for cancer immunotherapy.

Natural killer (NK) cells, which are key components of the innate immune response, are crucial for ensuring the efficacy of vaccines as they rapidly eliminate infected cells and enhance the adaptive immune response, ensuring robust and lasting protection. In this report, we investigated the effect of Cladophora wrightiana var. minor (CW) extract, a marine alga, in activating NK cells, as an adjuvant to inactivated A/Puerto Rico/8/34 H1N1 influenza vaccine (iPR8). In vitro, CW extract significantly enhanced the level of activation markers CD69 and CD107a on NK cells and triggered intracellular secretion of interferon gamma (IFN‐γ) and granzyme B (GrB), indicating effective NK cell stimulation and cytotoxic function. In vivo, CW extract promoted substantial NK cell recruitment and activation, resulting in higher NK cell populations and elevated post‐immunization levels of activation markers. Additionally, CW extract increased IFN‐γ and GrB production in CD8+ T cells, highlighting its broader impact on the immune response. We also found direct evidence that CW‐activated NK cells and dendritic cells (DCs) interacted with and induced the activation of immature DCs and resting NK cells, respectively. These findings suggest that CW extract is a promising adjuvant for nasal vaccines, enhancing cellular immunity by activating NK cells and supporting interactions with DCs and CD8+ T cells. Cladophora wrightiana var. minor (CW) extract, administered as an adjuvant with inactivated influenza virus (iPR8), stimulates both innate and adaptive immune responses. CW enhances NK cell activation, cytotoxic function, and reciprocal crosstalk with dendritic cells, while also promoting CD8+ T cell responses and antigen‐specific IgG production. These findings support CW as a potent nasal vaccine adjuvant capable of boosting protective immunity. https://app.biorender.com/illustrations/6893f7d09e3fc89e9d953f76?slideId=2a6a42b6‐a3d9‐400a‐b839‐fa297b3108c5.

BackgroundCD24 plays a crucial role not only in promoting tumor progression and metastasis but also in modulating macrophage-mediated anti-tumor immunity. However, its impact on the immune landscape of the tumor microenvironment (TME) remains unexplored. Here, we investigated the role of CD24a, the murine CD24 gene, in tumor progression and TME immune dynamics in a murine triple-negative breast cancer (TNBC) model.MethodsClustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 knockout technology was employed to generate CD24a knockout in the murine TNBC cell line 4T1. Flow cytometry was utilized to analyze the immune cell populations, including myeloid-derived suppressor cells (MDSCs), natural killer cells, T cells, and macrophages, within tumors, spleens, and bone marrow in the orthotopic mouse 4T1 breast cancer model. Immunofluorescence (IF) staining was used to detect the immune cells in tumor sections. High-speed confocal was used to perform three-dimensional (3D) mapping of immune cells in the 4T1 orthotopic tumors.ResultsKnocking out CD24a significantly reduced tumor growth kinetics and prolonged mouse survival in vivo. Flow cytometry and IF analysis of tumor samples revealed that CD24a loss significantly promoted the infiltration of M1 macrophages and cytotoxic CD8+ T cells into the TME while reducing the recruitment and expansion of granulocytic MDSCs (gMDSCs). In vitro coculture experiments showed that CD24a deficiency significantly enhanced macrophage‐mediated phagocytosis and CD8⁺ T cell-mediated cytotoxicity, effects that were partially reversed by re‐expression of CD24a. Moreover, in vivo depletion of macrophages and CD8+ T cells reverted the delayed tumor growth caused by CD24a knockout, underscoring their critical role in tumor growth suppression associated with CD24a knockout. 3D mapping of immune cells in the TME confirmed the anti-tumor immune landscape in the CD24a knockout 4T1 tumors. Furthermore, in vitro analysis showed that CD24a loss upregulated macrophage colony-stimulating factor expression while suppressed levels of CXCL1, CXCL5, and CXCL10, chemokines known to recruit gMDSCs, further providing a molecular basis for enhanced macrophage recruitment and diminished gMDSC accumulation.ConclusionsOur findings suggest that CD24a may regulate immune suppression within the TNBC TME. Targeting CD24a enhances macrophage- and CD8⁺ T cell-mediated anti-tumor immune responses and is associated with a shift in the TME toward a more immunogenic state, thereby suppressing tumor growth. These results may support CD24 as a promising immunotherapeutic target for TNBC.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12929-025-01165-3.