Molecular Mechanism of Tumor Cell Immune Escape Mediated by CD24/Siglec-10

Yin, Shanshan; Gao, Feng‐Hou

doi:10.3389/fimmu.2020.01324

Cited by 72 publications

(56 citation statements)

References 108 publications

(190 reference statements)

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“…Siglec-G/10 is the receptor of CD24 and is broadly expressed on B cells, dendritic cells and monocyte subsets. 25 CD24 interacts with Siglec-10 to negatively regulate the immune response to proteins released by damaged cells. 26 At present, the study has proved that CD24–Siglec-10 exists in regions of fetal–maternal interactions and CD24 indicated a possible role in mediating immune tolerance at the fetal–maternal boundary.…”

Section: Discussionmentioning

confidence: 99%

CD24 Contributes to Treatment Effect in ABC-DLBCL Patients with R-CHOP Resistance

Qiao¹,

Li²,

Zhang³

et al. 2021

PGPM

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Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma and of which the prognosis of activated B-cell-like (ABC) subtype is poor. Although R-CHOP significantly improves the survival of patients with DLBCL, 20% to 40% of patients were resistant to R-CHOP therapy. Thus, screening for candidate therapeutic targets for R-CHOP resistant patients is urgent. The previous researches have shown that CD24 is related to the development, invasion, and metastasis of cancer. Our project aims to clarify the relationship between CD24 and ABC-DLBCL. Patients and Methods: The expression of CD24 mRNA in 118 ABC-DLBCL cases treated with R-CHOP was detected by RNAscope, and the relationship between CD24 expression and R-CHOP treatment response was analyzed. The correlation between CD24 expression and treatment efficiency was further analyzed by data downloaded from the Gene Expression Omnibus (GEO) database. The association between CD24 expression and immune response was conducted using Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) methodology and Gene Ontology (GO) biological process (BP) analysis. Results: The positive expression rate of CD24 mRNA in ABC-DLBCL patients was 38.1% (45/118). Complete Response (CR) rate was significantly higher in patients with CD24 high expression than those with CD24 low expression (P=0.039; 44.4% vs 26.0%). CR rate was significantly different between CD24 high and low expression groups in the analysis of GEO datasets (P=0.003; 83.2% vs 58.0%). The CD24 high expression patients had significantly lower proportions of T cells and nonspecific immune cells in the CIBERSORT analysis. In addition, T−helper 2 cell differentiation and monocyte chemotaxis were repressed in CD24 high expression group in the GO BP analysis. Conclusion: CD24 was correlated with better R-CHOP treatment response and tumor immunosuppression in ABC-DLBCL. CD24 may be a promising signal in treatment and prognosis evaluation in ABC-DLBCL patients.

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Section: Discussionmentioning

confidence: 99%

CD24 Contributes to Treatment Effect in ABC-DLBCL Patients with R-CHOP Resistance

Qiao¹,

Li²,

Zhang³

et al. 2021

PGPM

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“…SIGLEC10 was among the top 10 transcripts of its category (others) that were uniquely and significantly downregulated in Mob-MDM(LPS/IFNγ). The interaction between sialic acid-binding Ig-like lectin 10 (Siglec-10) on the surface of Mϕs with CD24, commonly overexpressed on numerous human cancers, has been previously described to be involved in the suppression of Mϕ-mediated immune responses to cancer [51]. Targeting the CD24-Siglec-10 signaling axis stands as a promising approach for cancer immunotherapy whereby blocking Siglec-10 on human MDMs resulted in a significant increase in the phagocytic capacity of tumor cells [52].…”

Section: Discussionmentioning

confidence: 99%

Cytokine/Chemokine Release Patterns and Transcriptomic Profiles of LPS/IFNγ-Activated Human Macrophages Differentiated with Heat-Killed Mycobacterium obuense, M-CSF, or GM-CSF

Bazzi

El-Darzi

McDowell

et al. 2021

IJMS

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Macrophages (Mφs) are instrumental regulators of the immune response whereby they acquire diverse functional phenotypes following their exposure to microenvironmental cues that govern their differentiation from monocytes and their activation. The complexity and diversity of the mycobacterial cell wall have empowered mycobacteria with potent immunomodulatory capacities. A heat-killed (HK) whole-cell preparation of Mycobacterium obuense (M. obuense) has shown promise as an adjunctive immunotherapeutic agent for the treatment of cancer. Moreover, HK M. obuense has been shown to trigger the differentiation of human monocytes into a monocyte-derived macrophage (MDM) type named Mob-MDM. However, the transcriptomic profile and functional properties of Mob-MDMs remain undefined during an activation state. Here, we characterized cytokine/chemokine release patterns and transcriptomic profiles of lipopolysaccharide (LPS)/interferon γ (IFNγ)-activated human MDMs that were differentiated with HK M. obuense (Mob-MDM(LPS/IFNγ)), macrophage colony-stimulating factor M-MDM(LPS/IFNγ)), or granulocyte/macrophage colony-stimulating factor (GM-MDM(LPS/IFNγ)). Mob-MDM(LPS/IFNγ) demonstrated a unique cytokine/chemokine release pattern (interleukin (IL)-10low, IL-12/23p40low, IL-23p19/p40low, chemokine (C-x-C) motif ligand (CXCL)9low) that was distinct from those of M-MDM(LPS/IFNγ) and GM-MDM(LPS/IFNγ). Furthermore, M-MDM(LPS/IFNγ) maintained IL-10 production at significantly higher levels compared to GM-MDM(LPS/IFNγ) and Mob-MDM(LPS/IFNγ) despite being activated with M1-Mφ-activating stimuli. Comparative RNA sequencing analysis pointed to a distinct transcriptome profile for Mob-MDM(LPS/IFNγ) relative to both M-MDM(LPS/IFNγ) and GM-MDM(LPS/IFNγ) that comprised 417 transcripts. Functional gene-set enrichment analysis revealed significant overrepresentation of signaling pathways and biological processes that were uniquely related to Mob-MDM(LPS/IFNγ). Our findings lay a foundation for the potential integration of HK M. obuense in specific cell-based immunotherapeutic modalities such as adoptive transfer of Mφs (Mob-MDM(LPS/IFNγ)) for cancer treatment.

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“…CD24 meets the criteria of a good imaging biomarker, as it is almost uniquely expressed on tumor cells and predominantly physiologically In addition, CD24 plays a role in immune inhibition. Aside from its interaction with P-selectin, CD24 interacts with sialic-acid-binding Ig-like lectin 10 (Siglec-10), a receptor expressed on tumor-associated macrophages (TAMs) [16,104]. Cancer cells evade phagocytosis by TAMs through the expression of the "don't eat me"-receptors CD47, PD-L1, MHC-I β2 microglobulin subunit (b2m), and CD24.…”

Section: Discussionmentioning

confidence: 99%

The Emerging Role of CD24 in Cancer Theranostics—A Novel Target for Fluorescence Image-Guided Surgery in Ovarian Cancer and Beyond

Kleinmanns

Fosse

Bjørge

et al. 2020

JPM

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Complete cytoreductive surgery is the cornerstone of the treatment of epithelial ovarian cancer (EOC). The application of fluorescence image-guided surgery (FIGS) allows for the increased intraoperative visualization and delineation of malignant lesions by using fluorescently labeled targeting biomarkers, thereby improving intraoperative guidance. CD24, a small glycophosphatidylinositol-anchored cell surface receptor, is overexpressed in approximately 70% of solid cancers, and has been proposed as a prognostic and therapeutic tumor-specific biomarker for EOC. Recently, preclinical studies have demonstrated the benefit of CD24-targeted contrast agents for non-invasive fluorescence imaging, as well as improved tumor resection by employing CD24-targeted FIGS in orthotopic patient-derived xenograft models of EOC. The successful detection of miniscule metastases denotes CD24 as a promising biomarker for the application of fluorescence-guided surgery in EOC patients. The aim of this review is to present the clinical and preclinically evaluated biomarkers for ovarian cancer FIGS, highlight the strengths of CD24, and propose a future bimodal approach combining CD24-targeted fluorescence imaging with radionuclide detection and targeted therapy.

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Molecular Mechanism of Tumor Cell Immune Escape Mediated by CD24/Siglec-10

Cited by 72 publications

References 108 publications

CD24 Contributes to Treatment Effect in ABC-DLBCL Patients with R-CHOP Resistance

CD24 Contributes to Treatment Effect in ABC-DLBCL Patients with R-CHOP Resistance

Cytokine/Chemokine Release Patterns and Transcriptomic Profiles of LPS/IFNγ-Activated Human Macrophages Differentiated with Heat-Killed Mycobacterium obuense, M-CSF, or GM-CSF

The Emerging Role of CD24 in Cancer Theranostics—A Novel Target for Fluorescence Image-Guided Surgery in Ovarian Cancer and Beyond

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