CD24 is a Potential Biomarker for Prognosis in Human Breast Carcinoma

Xuan, Jianhua; Cui, Xiangrong; Liang, Hongping; Hao, Chonghua; Zy, Yang; Li, Xiaogai; Yang, Xin; Han, Chongyang

doi:10.1159/000491667

Cited by 37 publications

(22 citation statements)

References 37 publications

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“…Remarkably, AZA also down-regulated genes that encode CD24, which is over-expressed in many cancers. 28 GSEA also highlighted pathways with previously underappreciated roles in regulating the responses of leukemia cells to cytotoxic T lymphocyte (CTL)-mediated killing (Supplementary Table S1). Pre-treatment with AZA did not modulate target CD19 gene expression or the expression of genes encoding PD-L1 or PD-L2, which is consistent with flow cytometry data.…”

Section: Gene Expression In Leukemia Cells Isolated From Mice Primed With Azamentioning

confidence: 99%

Priming Leukemia with 5-Azacytidine Enhances CAR T Cell Therapy

Xu¹,

Tse²,

Yang³

et al. 2021

ITT

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Purpose Despite the success of chimeric antigen receptor (CAR) T cells in clinical studies, a significant proportion of responding patients eventually relapsed, with the latter correlating with low CAR T cell expansion and persistence. Methods and Results Using patient-derived xenograft (PDX) mouse models of CD19 + B cell acute lymphoblastic leukemia (B-ALL), we show that priming leukemia-bearing mice with 5-azacytidine (AZA) enhances CAR T cell therapy. AZA given 1 day prior to CAR T cell infusion delayed leukemia growth and promoted CAR T cell expansion and effector function. Priming leukemia cells with AZA increased CAR T cell/target cell conjugation and target cell killing, promoted CAR T cell divisions and expanded IFNγ + effector T cells in co-cultures with CD19 + leukemia Nalm-6 and Raji cells. Transcriptome analysis revealed activation of diverse immune pathways in leukemia cells isolated from mice treated with AZA. We propose that epigenetic priming with AZA induces transcriptional changes that sensitize tumor cells to subsequent CAR T cell treatment. Among the candidate genes up-regulated by AZA is TNFSF4 which encodes OX40L, one of the strongest T cell co-stimulatory ligands. OX40L binds OX40, the TNF receptor superfamily member highly specific for activated T cells. TNFSF4 is heterogeneously expressed in a panel of pediatric PDXs, and high TNFSF4 expression correlated with increased CAR T cell numbers identified in co-cultures with individual PDXs. High OX40L expression in Nalm-6 cells increased their susceptibility to CAR T cell killing while OX40L blockade reduced leukemia cell killing. Conclusion We propose that treatment with AZA activates OX40L/OX40 co-stimulatory signaling in CAR T cells. Our data suggest that the clinical use of AZA before CAR T cells could be considered.

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Section: Gene Expression In Leukemia Cells Isolated From Mice Primed With Azamentioning

confidence: 99%

Priming Leukemia with 5-Azacytidine Enhances CAR T Cell Therapy

Xu¹,

Tse²,

Yang³

et al. 2021

ITT

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“…There is extensive research on the correlation between CD24 and cancer [ 8 , 9 , 10 , 11 , 12 ]. Many studies point to the role of CD24 in tumor growth and cancer progression [ 6 , 13 , 14 , 15 ]. CD24 expression has been evaluated as a prognostic marker of poor survival in many types of cancer [ 14 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…Many studies point to the role of CD24 in tumor growth and cancer progression [ 6 , 13 , 14 , 15 ]. CD24 expression has been evaluated as a prognostic marker of poor survival in many types of cancer [ 14 , 16 , 17 , 18 ]. CD24 is highly expressed in ovarian, breast, prostate, bladder, kidney, non-small cell, colorectal, and other human cancers [ 11 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Predictors of the CD24/CD11b Biomarker among Healthy Subjects

Shapira

Aiger

Ohayon

et al. 2021

JPM

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The CD24 gene has raised considerable interest in tumor biology as a new prognostic factor and a biomarker for the early detection of cancer. There are currently no studies that assess predictors of CD24 in blood tests among healthy individuals. Our aims were (1) to evaluate predictors of the CD24/CD11b biomarker among healthy subjects and (2) to assess CD24/CD11b levels of participants with and without benign tumors. Our cohort included 1640 healthy subjects, aged 20–85, recruited at the Health Promotion and Integrated Cancer Prevention Center (ICPC) in the Tel Aviv Medical Center. Eligible subjects completed a detailed questionnaire on medical history and other epidemiologic information. CD24/CD11b expression in peripheral blood leukocytes (PBLs) obtained from blood samples of participants was analyzed by flow cytometry. Our results showed that the average levels of CD24/CD11b in healthy patients (22.8 ± 9.3) was statistically significant lower compared to subjects with benign cancers (26.1 ± 10.5, p < 0.001). Our multivariable analysis demonstrated that elevated levels of CRP (coefficient β: 1.98, p = 0.011) were significantly associated with high levels of CD24/CD11b expression among healthy participants. Other risk factors of cancer were not associated with elevated CD24 levels among healthy subjects. In conclusion, our findings may assist in further development and optimization of the CD24/CD11b biomarker to serve as a cancer screening test for early detection of cancer among the healthy population.

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“…CD24 is a highly glycosylated protein that is linked to membrane lipid raft microdomains via a glycosylphosphatidylinositol (GPI) anchor. Recent studies have shown that CD24 correlates with poor prognosis in many types of tumor tissues, including gliomas (Deng et al, 2012), hepatocellular carcinoma (HCC) (Wan et al, 2016), and breast cancer (Jing et al, 2018). Furthermore, CD24 may play a role in chemotherapy resistance in triple-negative breast cancer (TNBC) (Deng et al, 2017), HCC (Lu et al, 2018), and endometrial cancer (Ono et al, 2015), further implicating it as a potential drug target (Ono et al, 2015;Runz et al, 2008;Schabath et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy

Sun

Feng

et al. 2020

Molecular Oncology

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Retinoblastoma (RB) is the most common childhood malignant intraocular tumor. The clinical efficacy of vincristine (VCR) in the treatment of RB is severely limited by drug resistance. Here, we found that CD24, a GPI-anchored protein, was overexpressed in human RB tissues and RB cell lines, and was associated with the sensitivity of RB cells in response to VCR therapy. We demonstrated that CD24 plays a critical role in impairing RB sensitivity to VCR via regulating autophagy. Mechanistically, CD24 recruits PTEN to the lipid raft domain and regulates the PTEN/AKT/ mTORC1 pathway to activate autophagy. Lipid raft localization was essential for CD24 recruitment function. Collectively, our findings revealed a novel role of CD24 in regulating RB sensitivity to VCR and showed that CD24 is a potential target for improving chemotherapeutic sensitivity and RB patient outcomes. Shields, 2004). The treatment of RB is multimodal. Basic treatment methods are chemotherapy, radiation therapy, enucleation, and focal treatment including transpupillary thermotherapy, cryotherapy, and laser photocoagulation, all playing a vital role (Yanik et al., 2015). Recently, chemotherapy has become the most

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CD24 is a Potential Biomarker for Prognosis in Human Breast Carcinoma

Cited by 37 publications

References 37 publications

Priming Leukemia with 5-Azacytidine Enhances CAR T Cell Therapy

Priming Leukemia with 5-Azacytidine Enhances CAR T Cell Therapy

Predictors of the CD24/CD11b Biomarker among Healthy Subjects

CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy

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