SLAM-family receptors come of age as a potential molecular target in cancer immunotherapy

Farhangnia, Pooya; Ghomi, Shamim Mollazadeh; Mollazadehghomi, Shabnam; Nickho, Hamid; Akbarpour, Mahzad; Delbandi, Ali‐Akbar

doi:10.3389/fimmu.2023.1174138

Cited by 20 publications

(16 citation statements)

References 197 publications

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“…Thus, beside SLAMF9 involved in pDC homeostasis in a full organism (20), SLAMF7 and SLAMF8 emerge as paramount members of the SLAMF receptor family regulating pDC response to intracellular bacteria. The involvement of SLAMF7 and SLAMF8 extends beyond infectious diseases to cancer and autoimmunity (9, 56). Therefore, the concerted role of SLAMF7 and SLAMF8 in orchestrating human pDC responses against bacteria (Figure 5F) suggests that cell-specific blockade of these receptors may constitute a promising therapy to abate pDC activation and hyper-production of type I IFN during infection, as well as in autoimmune disorders and cancer.…”

Section: Discussionmentioning

confidence: 99%

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SLAMF7 and SLAMF8 receptors shape human plasmacytoid dendritic cell responses to intracellular bacteria

Pellegrini,

Keriel,

Gorvel

et al. 2024

Preprint

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Plasmacytoid dendritic cells (pDC), professional type I interferon (IFN) producing cells, have been implicated in host responses against bacterial infections. However, their role in host defense is debated and the operating molecular mechanisms are unknown. Certain Signaling Lymphocyte Activation Molecule Family (SLAMF) members act as microbial sensors and modulate immune functions in response to infection. Here by analyzing multiple human blood transcriptomic datasets, we report the involvement of SLAMF7 and SLAMF8 in many infectious diseases, with elevated levels associated with type I IFN responses in salmonellosis and brucellosis patients. We further identify SLAMF7 and SLAMF8 as key regulators of human pDC function. Silencing of these receptors hinders pDC maturation and abrogates cytokine production during infection with acute (Salmonella) or chronic (Brucella) inflammation-inducing bacteria. Mechanistically, we show that SLAMF7 and SLAMF8 signal through NF-κB, IRF7 and STAT-1, and limit mitochondrial ROS accumulation upon Salmonella infection. This SLAMF7/8-dependent control of mitochondrial ROS levels favors bacterial persistence and NF-κB activation. Overall, our results unravel essential shared roles of SLAMF7 and SLAMF8 in finely tuning human pDC responses to intracellular bacterial infections with high diagnosis and therapeutic perspectives.

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Section: Discussionmentioning

confidence: 99%

“…The Signaling Lymphocyte Activation Molecule Family (SLAMF) of cell surface glycoproteins comprises nine immunoreceptors widely expressed in myeloid and lymphoid cells (9), which have been implicated in diverse immune processes through homotypic interactions, but SLAMF2 and SLAMF4. Some of these receptors serve as microbial sensors.…”

Section: Introductionmentioning

confidence: 99%

SLAMF7 and SLAMF8 receptors shape human plasmacytoid dendritic cell responses to intracellular bacteria

Pellegrini,

Keriel,

Gorvel

et al. 2024

Preprint

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“…SLAMF2 and SLAMF4 have mainly been detected on T- and NK cells in tumors and may affect the ability of the immune system to control solid tumors. On the other hand, SLAM-family receptors, particularly SLAMF4, may be inhibitory or activatory in cells with SAP adaptor molecules, depending on the situation ( 63 ). Research on SLAMF3 remains limited.…”

Section: Discussionmentioning

confidence: 99%

“…However, targeting SLAMF receptors could also impact the normal immune response and increase the risk of infections due to their complex regulatory functions within the immune system ( 67 ). Therefore, it is crucial to take into consideration the potential risks associated with targeting SLAMF receptors and to take appropriate safety measures to minimize the potential toxicities, such as neutropenia, thrombocytopenia, and hepatotoxicity ( 63 ).…”

Section: Discussionmentioning

confidence: 99%

Signaling lymphocytic activation molecule family receptors as potential immune therapeutic targets in solid tumors

Gunes,

Rosen,

Shachar

et al. 2024

Front. Immunol.

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Recently, cancer immunotherapy has revolutionized cancer treatment. Various forms of immunotherapy have a manageable safety profile and result in prolongation of overall survival in patients with solid tumors, but only in a proportion of patients. Various factors in the tumor microenvironment play critical roles and may be responsible for this lack of therapeutic response. Signaling lymphocytic activation molecule family (SLAMF) members are increasingly being studied as factors impacting the tumor immune microenvironment. SLAMF members consist of nine receptors mainly expressed in immune cells. However, SLAMF receptors have also been detected in cancer cells, and they may be involved in a spectrum of anti-tumor immune responses. Here, we review the current knowledge of the expression of SLAMF receptors in solid tumors and tumor-infiltrating immune cells and their association with patient outcomes. Furthermore, we discuss the therapeutic potential of targeting SLAMF receptors to improve outcomes of cancer therapy in solid tumors. We believe the research on SLAMF receptor-targeted strategies may enhance anti-cancer immunity in patients with solid tumors and improve clinical outcomes.

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“…As a result, the anti-SLAMF7 antibody, Elotuzumab, is predominantly utilized in the treatment of multiple myeloma. 34 HS is associated with a hormonal imbalance, specifically involving sex hormones, and there is a higher prevalence of female patients with HS. Therefore, targeting the PI3 (Phosphoinositide 3-Kinase) pathway with Progesterone may serve as an adjunctive treatment approach for HS.…”

Section: Discussionmentioning

confidence: 99%

Discovering KYNU as a feature gene in hidradenitis suppurativa

Liang,

Yu,

Tang

et al. 2023

Int J Immunopathol Pharmacol

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Background Hidradenitis suppurativa (HS) is a chronic auto-inflammatory skin condition characterized by nodules, abscesses, and fistulae in skin folds. The underlying pathogenesis of HS remains unclear, and effective therapeutic drugs are limited. Methods We acquired mRNA expression profiles from the Gene Expression Omnibus (GEO) database and conducted differential expression analysis between control and HS samples using R software. Four machine learning algorithms (SVM, RF, ANN, and lasso) and WCGNA were utilized to identify feature genes. GO, KEGG, Metascape, and GSVA were utilized for the enrichment analysis. CIBERSORT and ssGSEA were employed to analyze immune infiltration. Results A total of 29 DEGs were identified, with the majority showing up-regulation in HS. Enrichment analysis revealed their involvement in immune responses and cytokine activities. KEGG analysis highlighted pathways such as IL-17 signaling, rheumatoid arthritis, and TNF signaling in HS. Immune infiltration analysis revealed the predominant presence of neutrophils, monocytes, and CD8 T cells. Machine learning algorithms and WCGNA identified KYNU as a feature gene associated with HS. We have also identified 59 potential drugs for HS based on the DEGs. Additionally, ceRNA network analysis identified the MUC19_hsa-miR-382-5p_KYNU pathway as a potential regulatory pathway. Conclusions KYNU emerged as a feature gene associated with HS, and the ceRNA network analysis identified the MUC19_hsa-miR-382-5p_KYNU pathway as a potential regulator.

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SLAM-family receptors come of age as a potential molecular target in cancer immunotherapy

Cited by 20 publications

References 197 publications

SLAMF7 and SLAMF8 receptors shape human plasmacytoid dendritic cell responses to intracellular bacteria

SLAMF7 and SLAMF8 receptors shape human plasmacytoid dendritic cell responses to intracellular bacteria

Signaling lymphocytic activation molecule family receptors as potential immune therapeutic targets in solid tumors

Discovering KYNU as a feature gene in hidradenitis suppurativa

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