LncRNA IL21-AS1 facilitates tumour progression by enhancing CD24-induced phagocytosis inhibition and tumorigenesis in ovarian cancer.

CD24 is overexpressed in various tumours and considered a regulator of cell migration, invasion, and proliferation. Recent studies have found that CD24 on ovarian cancer (OC) and triple-negative breast cancer cells interacts with the inhibitory receptor sialic-acid-binding Ig-like lectin 10 (Siglec-10) on tumour-associated macrophages (TAMs) to inhibit phagocytosis by macrophages. Because of its multiple roles in regulating the immune response and tumorigenesis, CD24 is a very promising therapeutic target. However, the regulatory mechanism of CD24 in OC remains unclear. Here, we found that the long noncoding RNA (lncRNA) IL21-AS1, which was upregulated in OC, inhibited macrophage-mediated phagocytosis and promoted OC cell proliferation and apoptosis inhibition. More importantly, after IL21-AS1 knockdown, a significant survival advantage was observed in mice engrafted with tumours. Mechanistically, we identified IL21-AS1 as a hypoxia-induced lncRNA. Moreover, IL21-AS1 increased HIF1α-induced CD24 expression under hypoxic conditions. In parallel, we found that IL21-AS1 acted as a competing endogenous RNA (ceRNA) for miR-561-5p to regulate CD24 expression. Finally, IL21-AS1 increased CD24 expression in OC and facilitated OC progression. Our findings provide a molecular basis for the regulation of CD24, thus highlighting a potential strategy for targeted treatment of OC.

Targeting the GPI transamidase subunit GPAA1 abrogates the CD24 immune checkpoint in ovarian cancer.

CD24 is frequently overexpressed in ovarian cancer and promotes immune evasion by interacting with its receptor Siglec10, present on tumor-associated macrophages, providing a "don't eat me" signal that prevents targeting and phagocytosis by macrophages. Factors promoting CD24 expression could represent novel immunotherapeutic targets for ovarian cancer. Here, using a genome-wide CRISPR knockout screen, we identify GPAA1 (glycosylphosphatidylinositol anchor attachment 1), a factor that catalyzes the attachment of a glycosylphosphatidylinositol (GPI) lipid anchor to substrate proteins, as a positive regulator of CD24 cell surface expression. Genetic ablation of GPAA1 abolishes CD24 cell surface expression, enhances macrophage-mediated phagocytosis, and inhibits ovarian tumor growth in mice. GPAA1 shares structural similarities with aminopeptidases. Consequently, we show that bestatin, a clinically advanced aminopeptidase inhibitor, binds to GPAA1 and blocks GPI attachment, resulting in reduced CD24 cell surface expression, increased macrophage-mediated phagocytosis, and suppressed growth of ovarian tumors. Our study highlights the potential of targeting GPAA1 as an immunotherapeutic approach for CD24+ ovarian cancers.

The safety and potential efficacy of exosomes overexpressing CD24 (EXO-CD24) in mild-moderate COVID-19 related ARDS.

INTRODUCTION: EXO-CD24 are exosomes genetically manipulated to over-express Cluster of Differentiation (CD) 24. It consists of two breakthrough technologies: CD24, the drug, as a novel immunomodulator that is smarter than steroids without any side effects, and exosomes as the ideal natural drug carrier. METHODS: A randomized, single blind, dose-finding phase IIb trial in hospitalized patients with mild to moderate Coronavirus disease 2019 (COVID-19) related Acute Respiratory Distress Syndrome (ARDS) was carried out in two medical centers in Athens. Patients received either 109 or 1010 exosome particles of EXO-CD24, daily, for five consecutive days and monitored for 28 days. Efficacy was assessed at day 7 among 91 patients who underwent randomization. The outcome was also compared in a post-hoc analysis with an income control group (n = 202) that fit the inclusion and exclusion criteria. RESULTS: The mean age was 49.4 (± 13.2) years and 74.4% were male. By day 7, 83.7% showed improved respiratory signs and 64% had better oxygen saturation (SpO2) (p < 0.05). There were significant reductions in all inflammatory markers, most notably in C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, fibrinogen and an array of cytokines. Conversely, levels of the anti-inflammatory cytokine Interleukin-10 (IL-10) were increased (p < 0.05). Of all the documented adverse events, none were considered treatment related. No drug-drug interactions were noted. Two patients succumbed to COVID-19. Post-hoc analysis revealed that EXO-CD24 patients exhibited greater improvements in clinical and laboratory outcomes compared to an observational income control group. CONCLUSIONS: EXO-CD24 presents a promising therapeutic approach for hyper-inflammatory state and in particular ARDS. Its unique combination of exosomes, as a drug carrier, and CD24, as an immunomodulator, coupled with inhalation administration, warrants further investigation in a larger, international, randomized, quadri-blind trial against a placebo.

Site-specific Antibody-Nitric Oxide Conjugate HN02 Possesses Improved Antineoplastic and Safety Properties.

Antibody-drug conjugates (ADCs) combine the high specificity of antibodies with the cytotoxicity of payloads and have great potential in pan-cancer immunotherapy. However, the current payloads for clinical uses have limited the therapeutic window due to their uncontrollable off-site toxicity. There is unmet needs to develop more potent ADC payloads with better safety and efficacy profiles. Nitric oxide (NO) is a special molecule that has low toxicity itself, which can kill tumor cells effectively when highly concentrated, has broad application prospects. Previously, we prepared for the first time an antibody-nitric oxide conjugate (ANC)-HN01, which showed inhibitory activity against hepatocellular carcinoma. However, the random conjugation method made HN01 highly heterogeneous and unstable. Here, we used site-specific conjugation-based engineered cysteine sites (CL-V211C) of anti-CD24 antibody to prepare a second-generation ANC with a drug-to-antibody ratio of 2. The homogeneous ANC, HN02 was stable in human plasma, shown in vitro bystander effect to neighboring cells and antiproliferative activity to CD24-targeted tumor cells. Compared with HN01, HN02 significantly prolonged the survival of tumor-bearing mice. In summary, we developed a stable and homogeneous site-specific conjugated ANC, which showed good antitumor activity and improved safety profile both in vitro and in vivo. This study provides new insight into the development of next generation of ADC candidates.

Unraveling the role of CD24 in Hepatocellular carcinoma: Involvement of inactivated Hippo signaling and SOX4-mediated regulation.

Hepatocellular carcinoma (HCC) is a prevalent type of liver cancer, and CD24 gene is reportedly involved in HCC progression. However, the precise regulatory mechanisms of CD24 in HCC remain unclear. In this study, we established a primary HCC mouse model and observed that CD24, induced by inactivation of the Hippo pathway, was highly expressed in HCC. Using a systematic molecular and genomic approach, we identified the Hippo-YAP1-SOX4 pathway as the mechanism through which YAP1 induces CD24 upregulation in HCC cells. CD24 knockdown significantly attenuated YAP1 activation-induced HCC. These findings shed light on the link between CD24 and HCC progression, particularly in the Hippo-inactivated subclass of HCC. Therefore, CD24 may serve as a potential target for specific treatment of this HCC subclass.

Checkpoint CD24 function on tumor and immunotherapy.

CD24 is a protein found on the surface of cells that plays a crucial role in the proliferation, invasion, and spread of cancer cells. It adheres to cell membranes through glycosylphosphatidylinositol (GPI) and is associated with the prognosis and survival rate of cancer patients. CD24 interacts with the inhibitory receptor Siglec-10 that is present on immune cells like natural killer cells and macrophages, leading to the inhibition of natural killer cell cytotoxicity and macrophage-mediated phagocytosis. This interaction helps tumor cells escape immune detection and attack. Although the use of CD24 as a immune checkpoint receptor target for cancer immunotherapy is still in its early stages, clinical trials have shown promising results. Monoclonal antibodies targeting CD24 have been found to be well-tolerated and safe. Other preclinical studies are exploring the use of chimeric antigen receptor (CAR) T cells, antibody-drug conjugates, and gene therapy to target CD24 and enhance the immune response against tumors. In summary, this review focuses on the role of CD24 in the immune system and provides evidence for CD24 as a promising immune checkpoint for cancer immunotherapy.

The response of CD27+CD38+ plasmablasts, CD24hiCD38hi transitional B cells, CXCR5-ICOS+PD-1+ Tph, Tph2 and Tfh2 subtypes to allergens in children with allergic asthma.

BACKGROUND: Allergic asthma is a type I allergic reaction mediated by serum Immunoglobulin E (IgE). B cell-mediated humoral immune response to allergens in the pathophysiology of allergic asthma have not been thoroughly elucidated. Peripheral helper T cells (Tph) and follicular helper T cells (Tfh) promote B cell differentiation and antibody production in inflamed tissues. OBJECTIVE: To investigate the roles of B cell subsets, Tph cell subsets and Tfh cell subsets in allergic immune responses. METHODS: Circulating B cell subsets, Tph cell subsets and Tfh cell subsets in 33 children with allergic asthma and 17 healthy children were analyzed using multicolor flow cytometry. The level of serum total IgE was also assessed. RESULTS: Our study found that CD27+CD38+ plasmablasts and CD24hiCD38hi transitional B cells increased and were correlated with serum total IgE level, CD27- naive B cells and CD24hiCD27+ B cells decreased in children with allergic asthma. CXCR5- Tph, CXCR5-ICOS+ Tph, CXCR5-ICOS+PD-1+ Tph, CXCR5+ICOS+ Tfh and CXCR5+ICOS+PD-1+ Tfh increased in children with allergic asthma. Further analysis showed increased Tph2, Tph17, Tfh2 and Tfh17 subtypes while decreased Tph1 and Tfh1 subtypes in children with allergic asthma. Most interestingly, Tph2 or Tfh2 subtypes had a positive correlation with serum total IgE level. CONCLUSION: Overall, these results provide insight into the allergens elicited B, Tph or Tfh cell response and identify heretofore unappreciated CD24hiCD38hi transitional B cells, CD24hiCD27+ B cells, CXCR5- Tph, CXCR5-ICOS+PD-1+ Tph, Tph2 subtypes and Tfh2 subtypes response to allergens.

VGLL1 stabilization of cytoplasmic TAZ promotes EGFR expression and maintains tumor initiating cells in breast cancer independent of TEAD.

Vestigial-like family member 1 (VGLL1) is one of the X-linked genes whose expression is elevated in basal-like breast cancer (BLBC) because of X-chromosome isodisomy. As an approach towards understanding its function, we performed correlation study using transcript data of breast cancer patients from cBioPortal for Cancer Genomics. Our analysis identified EGFR as the most correlated transcript with VGLL1. We demonstrate that VGLL1 promotes EGFR expression and increases the frequency of breast tumor initiating cells (CD44high/+CD24low/-). These findings are crucial because an elevated EGFR expression and high frequency of CD44high/+CD24low/- cells are defining features of BLBC, and we provide a new mechanistic insight into how their expressions are controlled. Importantly, VGLL1 regulation of EGFR and CD44high/+CD24low/- population is mediated by the hippo-transducer TAZ which exerts its oncogenic roles by binding and activating TEAD transcription factors. A crucial finding is that TEAD-binding domain of TAZ is dispensable for its regulation of EGFR and CD44high/+CD24low/- cells. Instead, VGLL1 stabilization of cytoplasmic TAZ is essential for these functions. Also, we show that VGLL1/TAZ restricts the surface expression of CD24 which contributes to the increased number of CD44high/+CD24low/- cells. In addition, we observed that VGLL1 represses AXL expression and suppresses claudin-low phenotype, and that is caused by the VGLL1 mediated nuclear expulsion of TAZ. Therefore, EGFR and AXL seem to represent two different breast tumor subtypes, and their differential expressions is controlled by VGLL1.

Role of CD44 and CD24 Expression on 2-years Disease Free Survival in Patients with Advanced Epithelial Ovarian Carcinoma.

OBJECTIVE: Ovarian cancer is one of the most common cancers with a high mortality rate worldwide. Despite optimal surgical therapy and chemotherapy, recurrence is still common. Cancer stem cells expressing CD44 and CD24 are thought to be contributing factors in recurrence. METHODS: A cohort retrospective study with survival analysis was carried out on advanced ovarian cancer patients who underwent optimal debulking surgery followed by 6 cycles of chemotherapy at Cipto Mangunkusumo General Hospital and Fatmawati General Hospital from January 2019 to March 2023. Immunohistochemical examination was performed on tumor tissue with CD44 and CD24 expression were assessed using the H-Score method then determined the cut off-point expression level using the ROC curve. Furthermore, the relationship between these expression levels with the disease-free survival was assessed using the survival curve. RESULTS: There were 48 subjects who were included in the study. There were high expression levels of CD44 in 47.9% and CD24 in 50% of cases. High CD44 expression had mean and median survival of 13.2 ± 1.8 and 11 months (HR 5.05, 95% CI 1.84- 13.85). High CD24 expression had mean and median survival of 13.5 ± 2.4 and 7 months (HR 7.73, 95% CI 2.58 - 23.15). The combination of the two high expressions had mean and median survival of 10.44 ± 1.88 and 7 months. CONCLUSION: High expression of CD44 and CD24 will shorten the disease-free survival of patients with advanced ovarian cancer.

CD24 negativity reprograms mitochondrial metabolism to PPARα and NF-κB-driven fatty acid ß-oxidation in triple-negative breast cancer.

CD24 is a well-characterized breast cancer (BC) stem cell (BCSC) marker. Primary breast tumor cells having CD24-negativity together with CD44-positivity is known to maintain high metastatic potential. However, the functional role of CD24 gene in triple-negative BC (TNBC), an aggressive subtype of BC, is not well understood. While the significance of CD24 in regulating immune pathways is well recognized in previous studies, the significance of CD24 low expression in onco-signaling and metabolic rewiring is largely unknown. Using CD24 knock-down and over-expression TNBC models, our in vitro and in vivo analysis suggest that CD24 is a tumor suppressor in metastatic TNBC. Comprehensive in silico gene expression analysis of breast tumors followed by lipidomic and metabolomic analyses of CD24-modulated cells revealed that CD24 negativity induces mitochondrial oxidative phosphorylation and reprograms TNBC metabolism toward the fatty acid beta-oxidation (FAO) pathway. CD24 silencing activates PPARα-mediated regulation of FAO in TNBC cells. Further analysis using reverse-phase protein array and its validation using CD24-modulated TNBC cells and xenograft models nominated CD24-NF-κB-CPT1A signaling pathway as the central regulatory mechanism of CD24-mediated FAO activity. Overall, our study proposes a novel role of CD24 in metabolic reprogramming that can open new avenues for the treatment strategies for patients with metastatic TNBC.

The Oncolytic Activity of Zika Viral Therapy in Human Neuroblastoma In Vivo Models Confers a Major Survival Advantage in a CD24-dependent Manner.

Neuroblastoma is the most common extracranial tumor, accounting for 15% of all childhood cancer-related deaths. The long-term survival of patients with high-risk tumors is less than 40%, and MYCN amplification is one of the most common indicators of poor outcomes. Zika virus (ZIKV) is a mosquito-borne flavivirus associated with mild constitutional symptoms outside the fetal period. Our published data showed that high-risk and recurrent neuroblastoma cells are permissive to ZIKV infection, resulting in cell type-specific lysis. In this study, we assessed the efficacy of ZIKV as an oncolytic treatment for high-risk neuroblastoma using in vivo tumor models. Utilizing both MYCN-amplified and non-amplified models, we demonstrated that the application of ZIKV had a rapid tumoricidal effect. This led to a nearly total loss of the tumor mass without evidence of recurrence, offering a robust survival advantage to the host. Detection of the viral NS1 protein within the tumors confirmed that a permissive infection preceded tissue necrosis. Despite robust titers within the tumor, viral shedding to the host was poor and diminished rapidly, correlating with no detectable side effects to the murine host. Assessments from both primary pretreatment and recurrent posttreatment isolates confirmed that permissive sensitivity to ZIKV killing was dependent on the expression of CD24, which was highly expressed in neuroblastomas and conferred a proliferative advantage to tumor growth. Exploiting this viral sensitivity to CD24 offers the possibility of its use as a prognostic target for a broad population of expressing cancers, many of which have shown resistance to current clinical therapies. SIGNIFICANCE: Sensitivity to the tumoricidal effect of ZIKV on high-risk neuroblastoma tumors is dependent on CD24 expression, offering a prognostic marker for this oncolytic therapy in an extensive array of CD24-expressing cancers.

Preclinical Repurposing of Sitagliptin as a Drug Candidate for Colorectal Cancer by Targeting CD24/CTNNB1/SOX4-Centered Signaling Hub.

Despite significant advances in treatment modalities, colorectal cancer (CRC) remains a poorly understood and highly lethal malignancy worldwide. Cancer stem cells (CSCs) and the tumor microenvironment (TME) have been shown to play critical roles in initiating and promoting CRC progression, metastasis, and treatment resistance. Therefore, a better understanding of the underlying mechanisms contributing to the generation and maintenance of CSCs is crucial to developing CSC-specific therapeutics and improving the current standard of care for CRC patients. To this end, we used a bioinformatics approach to identify increased CD24/SOX4 expression in CRC samples associated with poor prognosis. We also discovered a novel population of tumor-infiltrating CD24+ cancer-associated fibroblasts (CAFs), suggesting that the CD24/SOX4-centered signaling hub could be a potential therapeutic target. Pathway networking analysis revealed a connection between the CD24/SOX4-centered signaling, ß-catenin, and DPP4. Emerging evidence indicates that DPP4 plays a role in CRC initiation and progression, implicating its involvement in generating CSCs. Based on these bioinformatics data, we investigated whether sitagliptin, a DPP4 inhibitor and diabetic drug, could be repurposed to inhibit colon CSCs. Using a molecular docking approach, we demonstrated that sitagliptin targeted CD24/SOX4-centered signaling molecules with high affinity. In vitro experimental data showed that sitagliptin treatment suppressed CRC tumorigenic properties and worked in synergy with 5FU and this study thus provided preclinical evidence to support the alternative use of sitagliptin for treating CRC.

Bispecific BCMA/CD24 CAR-T cells control multiple myeloma growth.

Anti-multiple myeloma B cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies represent a promising treatment strategy with high response rates in myeloma. However, durable cures following anti-BCMA CAR-T cell treatment of myeloma are rare. One potential reason is that a small subset of minimal residual myeloma cells seeds relapse. Residual myeloma cells following BCMA-CAR-T-mediated treatment show less-differentiated features and express stem-like genes, including CD24. CD24-positive myeloma cells represent a large fraction of residual myeloma cells after BCMA-CAR-T therapy. In this work, we develop CD24-CAR-T cells and test their ability to eliminate myeloma cells. We find that CD24-CAR-T cells block the CD24-Siglec-10 pathway, thereby enhancing macrophage phagocytic clearance of myeloma cells. Additionally, CD24-CAR-T cells polarize macrophages to a M1-like phenotype. A dual-targeted BCMA-CD24-CAR-T exhibits improved efficacy compared to monospecific BCMA-CAR-T-cell therapy. This work presents an immunotherapeutic approach that targets myeloma cells and promotes tumor cell clearance by macrophages.

Targeting CD24/Siglec-10 signal pathway for cancer immunotherapy: recent advances and future directions.

The small, heavily glycosylated protein CD24 is primarily expressed by many immune cells and is highly expressed mostly in cancer cells. As one of the most crucial biomarkers of cancers, CD24 is frequently highly expressed in solid tumors, while tumor-associated macrophages express Siglec-10 at high levels, Siglec-10 and CD24 can interact on innate immune cells to lessen inflammatory responses to a variety of disorders. Inhibiting inflammation brought on by SHP-1 and/or SHP-2 phosphatases as well as cell phagocytosis by macrophages, the binding of CD24 to Siglec-10 can prevent toll-like receptor-mediated inflammation. Targeted immunotherapy with immune checkpoint inhibitors (ICI) has lately gained popularity as one of the best ways to treat different tumors. CD24 is a prominent innate immune checkpoint that may be a useful target for cancer immunotherapy. In recent years, numerous CD24/Siglec-10-related research studies have made tremendous progress. This study discusses the characteristics and workings of CD24/Siglec-10-targeted immunotherapy and offers a summary of current advances in CD24/Siglec-10-related immunotherapy research for cancer. We then suggested potential directions for CD24-targeted immunotherapy, basing our speculation mostly on the results of recent preclinical and clinical trials.

The Hippo-YAP signaling pathway drives CD24-mediated immune evasion in esophageal squamous cell carcinoma via macrophage phagocytosis.

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies in the world with poor prognosis. Despite the promising applications of immunotherapy, the objective response rate is still unsatisfactory. We have previously shown that Hippo/YAP signaling acts as a powerful tumor promoter in ESCC. However, whether Hippo/YAP signaling is involved in tumor immune escape in ESCC remains largely unknown. Here, we show that YAP directly activates transcription of the "don't eat me" signal CD24, and plays a crucial role in driving tumor cells to avoid phagocytosis by macrophages. Mechanistically, YAP regulates CD24 expression by interacting with TEAD and binding the CD24 promoter to initiate transcription, which facilitates tumor cell escape from macrophage-mediated immune attack. Our animal model data and clinical data show that YAP combined with CD24 in tumor microenvironment redefines the impact of TAMs on the prognosis of ESCC patients which will provide a valuable basis for precision medicine. Moreover, treatment with YAP inhibitor altered the distribution of macrophages and suppressed tumorigenesis and progression of ESCC in vivo. Together, our study provides a novel link between Hippo/YAP signaling and macrophage-mediated immune escape, which suggests that the Hippo-YAP-CD24 axis may act as a promising target to improve the prognosis of ESCC patients. A proposed model for the regulatory mechanism of Hippo-YAP-CD24-signaling axis in the tumor-associated macrophages mediated immune escape.

CD24+ decidual stromal cells: a novel heterogeneous population with impaired regulatory T cell induction and potential association with recurrent miscarriage.

OBJECTIVE: To explore the heterogeneity of CD24+ decidual stromal cells (DSCs) in patients with recurrent miscarriages (RMs). DESIGN: We have discerned that the expression of CD24 serves to differentiate two stable and functionally distinct lineages of DSCs. The heterogeneity of CD24+ DSCs has been scrutinized, encompassing variances in stromal markers, transcriptional profiles, metabolic activity, and immune regulation. SETTING: Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University; Shanghai Institute of Immunity and Infection, Chinese Academy of Science. PATIENTS: A total of 129 early decidual samples were obtained, comprising 36 from healthy donors and 93 from patients with RMs. Blood samples were collected before the surgical procedure. Paraffin-embedded segments from 20 decidual samples of patients with RMs were obtained. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The flow cytometry was used to quantify the expression of CD24+ DSCs in both healthy donors and patients with RMs, although it also evaluated the cellular heterogeneity. To ascertain the transcriptomic profiles of CD24+ DSCs by reanalyzing our single-cell transcriptomic data. Additionally, to measure the metabolomic activity of CD24+ DSCs from patients with RMs, ultraperformance liquid chromatography-mass spectrometry was employed. Through the implementation of a coculture system, we unraveled the role of CD24+ DSCs in immune regulation. RESULTS: Patients with RMs exhibit a notable enrichment of CD24+ DSCs, revealing a pronounced heterogeneity characterized by variations in stromal markers and transcriptional profiles. The heightened enrichment of CD24+ DSCs may play a pivotal role in triggering decidual inflammation and dysfunction in decidualization. Furthermore, CD24+ DSCs showed diverse metabolic activities and impeded the induction of naïve CD4+ T cells into regulatory T cells through the abundant secretion of 3-hydroxyisovaleric acid. Finally, our investigations have revealed that intraperitoneal administration of 3-hydroxyisovaleric acid in mouse models can elevate the risk of RM. CONCLUSION: We have successfully identified a disease-associated subset of CD24+ decidual stromal cells that could potentially contribute to the development of RM through the impairment of decidual immune tolerance. Targeting these specific CD24+ DSCs might hold promising prospects for therapeutic interventions in the clinical management of RM.

High Expression and Significance of Siglec10/CD24 in Unexplained Missed Abortion.

OBJECTIVE: To investigate the expression of Siglec10 and CD24 in normal early pregnancy and missed abortion, and their significance in the maternal-fetal interface. METHODS: For our research, we employed Q-PCR and WB techniques to evaluate the traits and expression of Siglec10 and CD24 in the nonpregnant endometrium, as well as in the villus and decidua of women in their 6-10 weeks of normal early pregnancy and those who experienced missed abortion. Additionally, we utilized ELISA to determine the levels of Siglec10 and CD24 in the peripheral blood of pregnancy, missed abortion, and non-pregnant individuals. T-test and ANOVA were used to compare groups. RESULTS: 1. Villous tissues in early pregnancy showed high expression of Siglec10 and CD24, with a significant increase in expression in the missed abortion group (P < 0.01).2. Nonpregnant endometrial tissue showed low expression of Siglec10 and CD24, while early pregnancy decidua showed high expression, with even higher expression in missed abortion (all P < 0.05).3. Serum levels of Siglec10 and CD24 in normal early pregnancy were significantly higher than non-pregnancy (P < 0.01). However, the missed abortion group showed significantly higher levels than normal pregnancy (P < 0.01).4. CD24 expression in serum of missed abortion increases with Siglec10 expression, indicating a significant positive correlation (r = 0.500, P < 0.01). CONCLUSION: Siglec10 and CD24 expression in villus, decidua, and peripheral blood are up-regulated in unexplained missed abortions than those of women with normal pregnancies. This suggests that the levels of serum Siglec10 and CD24 can be used as an effective predictor of missed abortion.

Targeting CD24 as a novel immunotherapy for solid cancers.

Cluster of differentiation 24 (CD24), a mucin-like highly glycosylated molecule has been extensively studied as a cancer stem cell marker in a variety of solid cancers. The functional role of CD24 is either fulfilled by combining with ligands or participating in signal transduction, which mediate the initiation and progression of neoplasms. Recently, CD24 was also described as an innate immune checkpoint with apparent significance in several types of solid cancers. Herein, we review the current understanding of the molecular fundamentals of CD24, the role of CD24 in tumorigenesis and cancer progression, the possibility as a promising therapeutic target and summarized different therapeutic agents or strategies targeting CD24 in solid cancers. Video Abstract.

Attenuated Salmonella carrying siRNA-CD24 improved the effect of oxaliplatin on HCC.

Oxaliplatin is a chemotherapy drug currently utilized in the treatment of advanced cancer patients. However, its tolerability poses a limitation to its clinical application. Studies have demonstrated that the presence of tumor-associated macrophages is positively correlated with poor prognosis in various solid tumors, including hepatocellular carcinoma (HCC), and is a significant factor contributing to oxaliplatin resistance. Therefore, targeting tumor-associated macrophages may be an effective strategy to improve the efficacy of oxaliplatin in the treatment of HCC patients. CD24 is a novel target for tumor therapy that can interact with the inhibitory receptor Siglec-10 on tumor-associated macrophages, transmitting immune inhibitory signals and inhibiting macrophage phagocytosis function. In this study, we utilized RNAi technology to inhibit the expression of CD24 in tumor cells and combined it with oxaliplatin, resulting in reduced tumor invasion, migration, and proliferation, as well as increased cell apoptosis. Furthermore, immunofluorescence and flow cytometry results indicated that both the single treatment group and combination treatment group enhanced the infiltration of immune cells. This study presents a novel approach to identifying combination therapy and targets for the clinical treatment of HCC with oxaliplatin.