Signaling lymphocytic activation molecules Slam and cancers: friends or foes?

Fouquet, Grégory; Marcq, Ingrid; Debuysscher, Véronique; Bayry, Jagadeesh; Singh, Amrathlal Rabbind; Bengrine, Abderrahmane; Nguyen‐Khac, Eric; Naassïla, Mickaël; Bouhlal, Hicham

doi:10.18632/oncotarget.24575

Cited by 19 publications

(15 citation statements)

References 93 publications

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“…PD-L1 is a well-known cancer immune checkpoint that when silenced in DCs augments expansion and function of antigen-specific T cells (30). SLAMF1 is overexpressed in myeloid cells from patients with Crohn's disease and in T lymphocytes from patients with rheumatoid arthritis (31). In regards to apoptosis, TNFRSF9 or 4-1BB acts as a survival factor in DCs (32) and the enzyme ADA abrogates the anti-inflammatory effects of adenosine present in apoptotic supernatants (33).…”

Section: Discussionmentioning

confidence: 99%

Long-Term Exposure to Inflammation Induces Differential Cytokine Patterns and Apoptosis in Dendritic Cells

et al. 2019

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The activation of dendritic cells (DCs) has profound implications and governs the control of adaptive immunity. However, long-term activation might drive exhaustion of immune cells and negatively affect functionality. Here, long-term vs. short-term exposure to bacterial lipopolysaccharide and interferon (IFN)γ was evaluated on human monocyte-derived DCs. Long-term activated DC1s began to undergo apoptosis concomitant with a profound TAM-receptor and efferocytosis-dependent induction of interleukin (IL)-10. Whereas, levels of IL-12p70 and IL-10 were positively correlated upon short-term activation, an inverse association occured upon long-term activation and, while short-term activated CD1a+ DCs were main producers of IL-12p70, CD1a− DCs were the main fraction that underwent apoptosis and released IL-10 upon long-term activation. Moreover, pre-apoptotic long-term activated DCs were no longer able to activate alloreactive IFNγ-responsive T cells present in peripheral blood mononuclear cells from healthy volunteers. The IFNγ response was mediated by IL-12p70, as a strong reduction in IFNγ was observed following blockade with an IL-12p70 neutralizing antibody. Finally, multiplex analysis of DC supernatants revealed a particular pattern of proteins associated with apoptosis, cancer and chronic inflammation partly overlapping with gold standard DCs well-known for their inability to secrete IL-12p70. In conclusion, long-term activated DC1s significantly changed their profile toward a non-functional, tumor-promoting and anti-inflammatory phenotype.

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Section: Discussionmentioning

confidence: 99%

Long-Term Exposure to Inflammation Induces Differential Cytokine Patterns and Apoptosis in Dendritic Cells

et al. 2019

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“…SLAMF1 is a cell surface receptor belonging to the signalling lymphocyte activation molecule family (SLAMF), itself a member of the immunoglobulin (Ig) superfamily. SLAMF1 is expressed on haematopoietic cells only and constitutes a self-ligand that triggers T-cell activation (Cannons, Tangye, & Schwartzberg, 2011;Fouquet et al, 2018). SLAMF1 is involved in immune responses against various pathogens (van Driel, Liao, Engel, & Terhorst, 2016).…”

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confidence: 99%

Omp25‐dependent engagement of SLAMF1 byBrucella abortusin dendritic cells limits acute inflammation and favours bacterial persistence in vivo

Degos

Hysenaj

González-Espinoza

et al. 2020

Cellular Microbiology

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The strategies by which intracellular pathogenic bacteria manipulate innate immunity to establish chronicity are poorly understood. Here, we show that Brucella abortus outer membrane protein Omp25 specifically binds the immune cell receptor SLAMF1 in vitro. The Omp25‐dependent engagement of SLAMF1 by B. abortus limits NF‐κB translocation in dendritic cells (DCs) with no impact on Brucella intracellular trafficking and replication. This in turn decreases pro‐inflammatory cytokine secretion and impairs DC activation. The Omp25‐SLAMF1 axis also dampens the immune response without affecting bacterial replication in vivo during the acute phase of Brucella infection in a mouse model. In contrast, at the chronic stage of infection, the Omp25/SLAMF1 engagement is essential for Brucella persistence. Interaction of a specific bacterial protein with an immune cell receptor expressed on the DC surface at the acute stage of infection is thus a powerful mechanism to support microbe settling in its replicative niche and progression to chronicity.

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“…19,20 Aside from IL-10, the signalling lymphocytic activation (SLAM) molecules are known for their roles in regulating immune responses, pathophysiology of neoplasm transformations and entry pathways of certain viruses. 21 Recently, SLAM molecules have come to the fore for their potential in diagnosis and therapy of various cancers. The signalling lymphocytic activation molecule family 1 (SLAMF1) in particular is the prototype member of the SLAM family of molecules that initiates signal transduction networks in many immune cells including T and B cells, dendritic cells, monocytesmacrophages, Natural Killer (NK) cells and Natural Killer T (NKT) cells that constitutively express them, thus modulating their activation and differentiation.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory patterns in plasma associate with hepatocellular carcinoma development in cured hepatitis C cirrhotic patients

et al. 2021

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Introduction The risk of hepatocellular carcinoma persists in some patients despite achieving sustained virologic response with current interferon-free direct-acting antiviral therapy for hepatitis C. The subject of an even higher carcinoma risk in this context has been reported and is currently being debated. The quest for understanding this paradox relative to the dynamics of inflammatory biomarkers in cirrhosis patients receiving antiviral therapy thus remains a subject of importance. Objective Here, we aimed at evaluating the effects of direct-acting antiviral therapy-induced hepatitis C cure on plasmatic markers of systemic inflammation measured before, during and after treatment. Specifically, soluble immune mediator phenotype associations that impact the odds of hepatocellular carcinoma development and the related changes that arise upon direct-acting antiviral-mediated hepatitis C clearance in cirrhosis patients was investigated. Methods Employing multiplex technology that measured up to 91 circulating biomarker proteins, we profiled the plasma soluble immune mediator concentrations of cirrhosis patients who developed post-treatment hepatocellular carcinoma and their respective negative controls, before and after direct-acting antiviral treatment. Results Elevated pre-therapy concentrations of specific soluble immune mediators including MCP-3, GDNF, CDCP1, IL-17C, IL-17A, SLAMF1, CCL11, FGF-5, LIF-R, IL10, IL-10RA, IL-15RA, beta NGF, CCL28, CCL25 and NT-3 distinguished patients who developed post-treatment hepatocellular carcinoma relative to those that did not. Particularly, GDNF, FGF-5 and IL-15RA displayed independent predictive biomarker attributes for delineating carcinoma emergence regardless of de novo or recurrence groupings. Upon successful therapy, the elevated pre-therapy soluble immune mediator establishment of the patients who eventually developed hepatocellular carcinoma stayed largely unperturbed whereas a panel of some 38 soluble immune mediators in the post-therapy carcinoma-free patients experienced significant ameliorations. Conclusions These results have considerable implications for delineating potential hepatocellular carcinoma emergence before initiating direct-acting antiviral therapy for hepatitis C in cirrhosis patients. They provide preliminary contribution to unravelling cases where the benefit of direct-acting antiviral therapies would be superior to the risk of developing carcinoma.

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Signaling lymphocytic activation molecules Slam and cancers: friends or foes?

Cited by 19 publications

References 93 publications

Long-Term Exposure to Inflammation Induces Differential Cytokine Patterns and Apoptosis in Dendritic Cells

Long-Term Exposure to Inflammation Induces Differential Cytokine Patterns and Apoptosis in Dendritic Cells

Omp25‐dependent engagement of SLAMF1 byBrucella abortusin dendritic cells limits acute inflammation and favours bacterial persistence in vivo

Inflammatory patterns in plasma associate with hepatocellular carcinoma development in cured hepatitis C cirrhotic patients

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