Decoding the Myeloid-Derived Suppressor Cells in Lymphoid Malignancies

Myeloid-derived suppressor cells (MDSCs) are immature myeloid precursors which emerged as a potent regulator of the immune system, exerting suppressive properties in diverse disease settings. In regards to cancer, MDSCs have an established role in solid tumors; however, their contribution to immune regulation during hematologic malignancies and particularly in lymphomas remains ill-defined. Herein focused on lymphoma, we discuss the literature on MDSC cells in all histologic types, and we also refer to lessons learned by animal models of lymphoma. Furthermore, we elaborate on future directions and unmet needs and challenges in the MDSC field related to lymphoma malignancies which may shed light on the complex nature of the immune system in malignancies.

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Crosstalk between myeloid‐derived suppressor cells and the immune system in prostate cancer

Journal of Leukocyte Biology ◽

10.1002/jlb.4ru0819-150rr ◽

2019 ◽

Vol 107 (1) ◽

pp. 43-56 ◽

Cited By ~ 4

Author(s):

Mohammad‐Javad Sanaei ◽

Loghman Salimzadeh ◽

Nader Bagheri

Keyword(s):

Prostate Cancer ◽

Immune System ◽

Suppressor Cells ◽

Myeloid Derived Suppressor Cells

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Myeloid-derived suppressor cells as regulators of the immune system

Nature Reviews Immunology ◽

10.1038/nri2506 ◽

2009 ◽

Vol 9 (3) ◽

pp. 162-174 ◽

Cited By ~ 3651

Author(s):

Dmitry I. Gabrilovich ◽

Srinivas Nagaraj

Keyword(s):

Immune System ◽

Suppressor Cells ◽

Myeloid Derived Suppressor Cells

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May critical molecular cross-talk between indoleamine 2,3-dioxygenase (IDO) and arginase during human aging be targets for immunosenescence control?

Immunity & Ageing ◽

10.1186/s12979-021-00244-x ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Ismael Dale Cotrim Guerreiro da Silva ◽

Dirce Maria Lobo Marchioni ◽

Antonio Augusto Ferreira Carioca ◽

Valquiria Bueno ◽

Gisele Wally Braga Colleoni

Keyword(s):

Immune System ◽

Aging Process ◽

Methylation Status ◽

Suppressor Cells ◽

Myeloid Derived Suppressor Cells ◽

Beta Oxidation ◽

Blood Concentrations ◽

Indoleamine 2,3 Dioxygenase ◽

Mass Spectrometry Technology ◽

Peripheral Blood Plasma

Abstract Background This study aimed to identify novel plasma metabolic signatures with possible clinical relevance during the aging process. A biochemical quantitative phenotyping platform, based on targeted electrospray ionization tandem mass spectrometry technology, was used for the identification of any eventual perturbed biochemical pathway by the aging process in prospectively collected peripheral blood plasma from 166 individuals representing the population of São Paulo city, Brazil. Results Indoleamine 2,3-dioxygenase (IDO) activity (Kyn/Trp) was significantly elevated with age, and among metabolites most associated with elevations in IDO, one of the strongest correlations was with arginase (Orn/Arg), which could also facilitate the senescence process of the immune system. Hyperactivity of IDO was also found to correlate with increased blood concentrations of medium-chain acylcarnitines, suggesting that deficiencies in beta-oxidation may also be involved in the immunosenescence process. Finally, our study provided evidence that the systemic methylation status was significantly increased and positively correlated to IDO activity. Conclusions In the present article, besides identifying elevated IDO activity exhibiting striking parallel association with the aging process, we additionally identified increased arginase activity as an underlying biochemical disturbance closely following elevations in IDO. Our findings support interventions to reduce IDO or arginase activities in an attempt to preserve the functionality of the immune system, including modulation of myeloid-derived suppressor cells (MDSCs), T cells, macrophages, and dendritic cells’ function, in old individuals/patients.

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The Role of Myeloid-Derived Suppressor Cells (MDSCs) in Graft-versus-Host Disease (GVHD)

Journal of Clinical Medicine ◽

10.3390/jcm10102050 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2050

Author(s):

Christos Demosthenous ◽

Ioanna Sakellari ◽

Vassiliki Douka ◽

Penelope Georgia Papayanni ◽

Achilles Anagnostopoulos ◽

...

Keyword(s):

Graft Versus Host Disease ◽

Suppressor Cells ◽

Hematologic Malignancies ◽

In Vivo Studies ◽

Myeloid Derived Suppressor Cells ◽

Hematopoietic Stem ◽

Host Disease ◽

Graft Versus Host ◽

Published Evidence

Background: Myeloid-derived suppressor cells (MDSCs) are implicated in the complex interplay involving graft-versus-leukemia (GVL) effects and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HCT) in hematologic malignancies. Methods: A review of literature through PubMed was undertaken to summarize the published evidence on the pathophysiology and clinical implications of MDSCs in allo-HCT. Literature sources published in English since 1978 were searched, using the terms Natural Suppressor (NS) cells, MDSCs, GVHD, and allo-HCT. Results: In vivo studies demonstrated that MDSCs derived from mobilization protocols could strongly suppress allo-responses mediated by T cells and enhance T-Reg activity, thus inhibiting GVHD toxicity. However, the influence of MDSCs on the GVL effect is not fully defined. Conclusions: The induction or maintenance of MDSC suppressive function would be advantageous in suppressing inflammation associated with GVHD. Pathways involved in MDSC metabolism and the inflammasome signaling are a promising field of study to elucidate the function of MDSCs in the pathogenesis of GVHD and translate these findings to a clinical setting.

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Dual Targeting of Multiple Myeloma Stem Cells and Myeloid-Derived Suppressor Cells for Treatment of Chemotherapy-Resistant Multiple Myeloma

Frontiers in Oncology ◽

10.3389/fonc.2021.760382 ◽

2021 ◽

Vol 11 ◽

Author(s):

Fatih M. Uckun

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

T Cell ◽

Disease Progression ◽

Suppressor Cells ◽

Lessons Learned ◽

Myeloid Derived Suppressor Cells ◽

Independent Manner ◽

Drug Candidates ◽

Delay Disease Progression

Here we review the insights and lessons learned from early clinical trials of T-cell engaging bispecific antibodies (BsABs) as a new class of biotherapeutic drug candidates with clinical impact potential for the treatment of multiple myeloma (MM). BsABs are capable of redirecting host T-cell cytotoxicity in an MHC-independent manner to malignant MM clones as well as immunosuppressive myeloid-derived suppressor cells (MDSC). T-cell engaging BsAB targeting the BCMA antigen may help delay disease progression in MM by destroying the MM cells. T-cell engaging BsAB targeting the CD38 antigen may help delay disease progression in MM by depleting both the malignant MM clones and the MDSC in the bone marrow microenvironment (BMME). BsABs may facilitate the development of a new therapeutic paradigm for achieving improved survival in MM by altering the immunosuppressive BMME. T-cell engaging BsiABs targeting the CD123 antigen may help delay disease progression in MM by depleting the MDSC in the BMME and destroying the MM stem cells that also carry the CD123 antigen on their surface.

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Transforming Growth Factor-Beta1 and Myeloid-Derived Suppressor Cells Interplay in Cancer

The Open Cancer Immunology Journal ◽

10.2174/1876401001706010001 ◽

2017 ◽

Vol 6 (1) ◽

pp. 1-14

Author(s):

Juan F. Santibanez ◽

Suncica Bjelica

Keyword(s):

Immune System ◽

Growth Factor ◽

Tumor Progression ◽

Cancer Progression ◽

Transforming Growth Factor Beta ◽

Cancer Metastasis ◽

Transforming Growth Factor ◽

Immune Surveillance ◽

Suppressor Cells ◽

Myeloid Derived Suppressor Cells

Background: Transforming growth factor-beta1 (TGF-β1) is a pleiotropic cytokine with a double role in cancer through its capacity to inhibit early stages of tumors while enhancing tumor progression at late stages of tumor progression. Moreover, TGF-β1 is a potent immunosuppressive cytokine within the tumor microenvironment that allows cancer cells to escape from immune surveillance, which largely contributes to the tumor progression. Method: It has been established that the cancer progression is commonly associated with increased number of Myeloid-derived suppressor cells (MDSC) that are a hallmark of cancer and a key mechanism of immune evasion. Result: MDSC represent a population of heterogeneous myeloid cells comprised of macrophages, granulocytes and dendritic cells at immature stages of development. MDSC promote tumor progression by regulating immune responses as well as tumor angiogenesis and cancer metastasis. Conclusion: In this review, we present an overview of the main key functions of both TGF-β1 and MDSC in cancer and in the immune system. Furthermore, the mutual contribution between TGF-β1 and MDSC in the regulation of immune system and cancer development will be analyzed.

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Immunotherapy Targeting Myeloid-Derived Suppressor Cells (MDSCs) in Tumor Microenvironment

Frontiers in Immunology ◽

10.3389/fimmu.2020.585214 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xidan Gao ◽

Hongshu Sui ◽

Shang Zhao ◽

Xingmei Gao ◽

Yanping Su ◽

...

Keyword(s):

Immune System ◽

Tumor Microenvironment ◽

Immune Escape ◽

Suppressor Cells ◽

Tumor Immunotherapy ◽

Therapeutic Effects ◽

Myeloid Derived Suppressor Cells ◽

Tumor Immune Escape ◽

New Directions ◽

Immature Myeloid Cells

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that accumulate in tumor-bearing hosts to reduce T cells activity and promote tumor immune escape in the tumor microenvironment (TME). The immune system in the TME can be stimulated to elicit an anti-tumor immune response through immunotherapy. The main theory of immunotherapy resides on the plasticity of the immune system and its capacity to be re-educated into a potent anti-tumor response. Thus, MDSCs within the TME became one of the major targets to improve the efficacy of tumor immunotherapy, and therapeutic strategies for tumor MDSCs were developed in the last few years. In the article, we analyzed the function of tumor MDSCs and the regulatory mechanisms of agents targeting MDSCs in tumor immunotherapy, and reviewed their therapeutic effects in MDSCs within the TME. Those data focused on discussing how to promote the differentiation and maturation of MDSCs, reduce the accumulation and expansion of MDSCs, and inhibit the function, migration and recruitment of MDSCs, further preventing the growth, invasion and metastasis of tumor. Those investigations may provide new directions for cancer therapy.

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Myeloid-derived suppressor cells at diagnosis may discriminate between benign and malignant ovarian tumors

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2019-000521 ◽

2019 ◽

Vol 29 (9) ◽

pp. 1381-1388 ◽

Cited By ~ 4

Author(s):

An Coosemans ◽

Thaïs Baert ◽

Jolien Ceusters ◽

Pieter Busschaert ◽

Chiara Landolfo ◽

...

Keyword(s):

Ovarian Cancer ◽

T Cells ◽

Immune System ◽

Natural Killer Cells ◽

Regulatory T Cells ◽

Natural Killer ◽

Immune Cells ◽

Suppressor Cells ◽

Myeloid Derived Suppressor Cells ◽

Killer Cells

BackgroundThe behavior of the immune system as a driver in the progression of ovarian cancer has barely been studied. Our knowledge is mainly limited to the intra-tumoral adaptive immune system. Because of the widespread metastases of ovarian cancer, an assessment of the circulating immune system seems more accurate.To demonstrate the presence of immune cells in blood samples of patients with ovarian neoplasms.MethodsIn this exploratory prospective cohort study, peripheral blood mononuclear cells were collected at diagnosis from 143 women, including 62 patients with benign cysts, 13 with borderline tumor, 41 with invasive ovarian cancer, and 27 age-matched healthy controls. Immune profile analyses, based on the presence of CD4 (cluster of differentiation), CD8, natural killer cells, myeloid-derived suppressor cells, and regulatory T cells, were performed by fluorescence activated cell sorting.ResultsIn a multivariable analysis, six immune cells (activated regulatory T cells, natural killer cells, myeloid-derived suppressor cells, monocytic myeloid-derived suppressor cells, exhausted monocytic myeloid-derived suppressor cells, and total myeloid cells) were selected as independent predictors of malignancy, with an optimism-corrected area under the receiver operating characteristic curve (AUC) of 0.858. In contrast, a profile based on CD8 and regulatory T cells, the current standard in ovarian cancer immunology, resulted in an AUC of 0.639.ConclusionsOur immune profile in blood suggests an involvement of innate immunosuppression driven by myeloid-derived suppressor cells in the development of ovarian cancer. This finding could contribute to clinical management of patients and in selection of immunotherapy.

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Cytokines

International Journal of Toxicology ◽

10.1177/1091581815584918 ◽

2015 ◽

Vol 34 (4) ◽

pp. 355-365 ◽

Cited By ~ 13

Author(s):

Thulasi Ramani ◽

Carol S. Auletta ◽

Daniel Weinstock ◽

Barbara Mounho-Zamora ◽

Patricia C. Ryan ◽

...

Keyword(s):

Immune System ◽

Inflammatory Diseases ◽

Safety Evaluation ◽

Lessons Learned ◽

Future Directions ◽

Cytokine Modulation ◽

The Many ◽

Factor Α ◽

Broad Role

Over the past 30 years, the world of pharmaceutical toxicology has seen an explosion in the area of cytokines. An overview of the many aspects of cytokine safety evaluation currently in progress and evolving strategies for evaluating these important entities was presented at this symposium. Cytokines play a broad role to help the immune system respond to diseases, and drugs which modulate their effect have led to some amazing therapies. Cytokines may be “good” when stimulating the immune system to fight a foreign pathogen or attack tumors. Other “good” cytokine effects include reduction of an immune response, for example interferon β reduction of neuron inflammation in patients with multiple sclerosis. They may be “bad” when their expression causes inflammatory diseases, such as the role of tumor necrosis factor α in rheumatoid arthritis or asthma and Crohn’s disease. Therapeutic modulation of cytokine expression can help the “good” cytokines to generate or quench the immune system and block the “bad” cytokines to prevent damaging inflammatory events. However, care must be exercised, as some antibody therapeutics can cause “ugly” cytokine release which can be deadly. Well-designed toxicology studies should incorporate careful assessment of cytokine modulation that will allow effective therapies to treat unmet needs. This symposium discussed lessons learned in cytokine toxicology using case studies and suggested future directions.

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