CD84 is a regulator of the immunosuppressive microenvironment in Multiple Myeloma

Lewinsky, Hadas; Gunes, Emine Gulsen; David, Keren; Radomir, Lihi; Kramer, Matthias P.; Pellegrino, Bianca; Perpinial, Michal; Chen, Jing; He, Ting; Mansour, Anthony G.; Teng, Kun yu; Bhattacharya, Supriyo; Caserta, Enrico; Troadec, Estelle; Lee, Peter; Feng, Mingye; Krishnan, Amrita; Rosenzweig, Michael; Yu, Jianhua; Caligiuri, Michael A.; Cohen, Yosef; Shevetz, Olga; Becker-Herman, Shirly; Pichiorri, Flavia; Rosen, Steven T.; Shachar, Idit

doi:10.1172/jci.insight.141683

Cited by 29 publications

(32 citation statements)

References 53 publications

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“…The expression of MIF was associated with stronger suppression of T-cell proliferation ( Zhang et al, 2017 ). MIF induces the expression of CD84, which is a regulator of the immunosuppressive microenvironment in MM ( Lewinsky et al, 2021 ). The TNFRSF14 is the marker for the drug response prediction of melphalan ( Liu et al, 2021 ), which was used in the first line of therapy of MM ( Buda et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Cellular Interaction Analysis Characterizing Immunosuppressive Microenvironment Functions in MM Tumorigenesis From Precursor Stages

Liu

Zhang²,

et al. 2022

Front. Genet.

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Cell–cell interaction event (CCEs) dysregulation may relate to the heterogeneity of the tumor microenvironment (TME) and would affect therapeutic responses and clinical outcomes. To reveal the alteration of the immune microenvironment in bone marrow from a healthy state to multiple myeloma (MM), scRNA-seq data of the four states, including healthy state normal bone marrow (NBM) and three disease states (MGUS, SMM, and MM), were collected for analysis. With immune microenvironment reconstruction, the cell types, including NK cells, CD8+ T cells, and CD4+ T cells, with a higher percentage in disease states were associated with prognosis of MM patients. Furthermore, CCEs were annotated and dysregulated CCEs were identified. The number of CCEs were significantly changed between disease states and NBM. The dysregulated CCEs participated in regulation of immune cell proliferation and immune response, such as MIF-TNFRSF14 interacted between early B cells and CD8+ T cells. Moreover, CCE genes related to drug response, including bortezomib and melphalan, provide candidate therapeutic markers for MM treatment. Furthermore, MM patients were separated into three risk groups based on the CCE prognostic signature. Immunoregulation-related differentiation and activation of CD4+ T cells corresponded to the progression status with moderate risk. These results provide a comprehensive understanding of the critical role of intercellular communication in the immune microenvironment over the evolution of premalignant MM, which is related to the tumorigenesis and progression of MM, which moreover, suggests a way of potential target selection for clinical intervention.

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Section: Discussionmentioning

confidence: 99%

Cellular Interaction Analysis Characterizing Immunosuppressive Microenvironment Functions in MM Tumorigenesis From Precursor Stages

Liu

Zhang²,

et al. 2022

Front. Genet.

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“…CD84, a member of the signaling lymphocyte activation molecule (SLAM) family, is expressed by hematopoietic cells and modulates immune responses. CD84 has been shown to be expressed by both PMN-MDSC and M-MDSC in patients with various cancers and in tumor-bearing mice (15,16).…”

Section: Mdsc: Origin Phenotype and Functionmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells: The Expanding World of Helminth Modulation of the Immune System

2022

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Infection with helminths or parasitic worms are highly prevalent worldwide especially in developing regions. Helminths cause chronic infections that are associated with suppression of immune responses to unrelated pathogens, vaccines, and by-stander antigens responsible for dysregulated immune responses as occurs in diseases such as allergies. Helminths use multiple mechanisms to modulate the immune system to evade the highly polarized type 2 immune response required to expel adult worms and for immunity to reinfection. Anthelmintic drugs are efficient in reducing adult worm burdens in helminth-infected individuals, but resistance to these drugs is rapidly increasing and vaccines against these pathogens are not available. Emerging evidence indicate that helminths induce myeloid-derived suppressor cells (MDSC), originally described in tumor-bearing mice and cancer patients. MDSC are a heterogenous population of immature cells that consist of two distinct sub-populations, polymorphonuclear (PMN)-MDSC and monocytic (M)-MDSC based on morphology and phenotype. MDSC suppress the function of T cells and other innate and adaptive immune cells including NK cells and B cells. During cancer or infection with bacteria or viruses, there is marked expansion of MDSC. Furthermore, the frequencies of MDSC correlate inversely with the prognosis and survival of tumor-bearing hosts as well as bacterial and viral burdens, persistence, and outcome in infected hosts. Currently, there is a paucity of data on MDSC and helminth infections. Here, we provide a survey of the evidence accumulated so far that overall support a role for MDSC in modulating immune responses during helminth infections. We review data from studies in various helminths, including those that infect humans. Finally, we summarize the progress to date in understanding the role of MDSC in helminth infections and briefly discuss potential host-directed strategies to target MDSC-mediated suppression of immune responses to helminths in favor of development of immunity to eliminate adult worms and possibly induce protection against reinfection.

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“…MIF interacts with its receptor CD74 to activate the IFNγ-JAK-STAT pathway, resulting in significant upregulation of PD-L1 in melanoma cells, which aids in tumor cell escape from the immune response and maintenance of immunosuppressive TME [ 219 ]. Data from a recent study indicate that MIF secreted by MM cells augments CD84 expression in TME, leading to upregulation of PD-L1 on MDSCs and suppression of T cells function, consequently promoting MM progression [ 220 ]. Neutralization of MIF is reported to inhibit PD-L1 expression in colon cancer-bearing mice, thereby suppressing tumor progression [ 128 ].…”

Section: Tumor-promoting Effects and Related Mechanisms Of Ta-mscs Ta...mentioning

confidence: 99%

TA-MSCs, TA-MSCs-EVs, MIF: their crosstalk in immunosuppressive tumor microenvironment

et al. 2022

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As an important component of the immunosuppressive tumor microenvironment (TME), it has been established that mesenchymal stem cells (MSCs) promote the progression of tumor cells. MSCs can directly promote the proliferation, migration, and invasion of tumor cells via cytokines and chemokines, as well as promote tumor progression by regulating the functions of anti-tumor immune and immunosuppressive cells. MSCs-derived extracellular vesicles (MSCs-EVs) contain part of the plasma membrane and signaling factors from MSCs; therefore, they display similar effects on tumors in the immunosuppressive TME. The tumor-promoting role of macrophage migration inhibitory factor (MIF) in the immunosuppressive TME has also been revealed. Interestingly, MIF exerts similar effects to those of MSCs in the immunosuppressive TME. In this review, we summarized the main effects and related mechanisms of tumor-associated MSCs (TA-MSCs), TA-MSCs-EVs, and MIF on tumors, and described their relationships. On this basis, we hypothesized that TA-MSCs-EVs, the MIF axis, and TA-MSCs form a positive feedback loop with tumor cells, influencing the occurrence and development of tumors. The functions of these three factors in the TME may undergo dynamic changes with tumor growth and continuously affect tumor development. This provides a new idea for the targeted treatment of tumors with EVs carrying MIF inhibitors.

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CD84 is a regulator of the immunosuppressive microenvironment in Multiple Myeloma

Cited by 29 publications

References 53 publications

Cellular Interaction Analysis Characterizing Immunosuppressive Microenvironment Functions in MM Tumorigenesis From Precursor Stages

Cellular Interaction Analysis Characterizing Immunosuppressive Microenvironment Functions in MM Tumorigenesis From Precursor Stages

Myeloid-Derived Suppressor Cells: The Expanding World of Helminth Modulation of the Immune System

TA-MSCs, TA-MSCs-EVs, MIF: their crosstalk in immunosuppressive tumor microenvironment

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