Protocol to assess the suppression of T-cell proliferation by human MDSC

Bruger, Annika M.; Vanhaver, Christophe; Bruderek, Kirsten; Amodio, Giada; Tavukçuoğlu, Ece; Esendağlı, Güneş; Gregori, Silvia; Brandau, Sven; Bruggen, Pierre van der

doi:10.1016/bs.mie.2019.05.046

Cited by 20 publications

(20 citation statements)

References 18 publications

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“…Considering the complex phenotype of human MDSCs and their rarity, it is recommended to isolate MDSCs using flow cytometry [6,45]. Magnetic selection of CD33 + or CD11b + cells could be used as an enrichment step, but preferably not as the principal method of isolation because MDSCs are rare, and the markers used are not exclusive.…”

Section: Mdscs In Humansmentioning

confidence: 99%

“…MDSC samples need to be processed carefully because granulocytes are easily activated by rough handling or cold temperatures. If and how this could affect the suppressive functions of PMN-MDSCs remains unclear [45]. Careful handling of MDSC samples is especially important when the cells are isolated from tissues other than blood, as it is unknown if and how mechanical and/or enzymatical digestion affects MDSC phenotypes or functions [46].…”

Section: Common Challenges In Handling Murine and Human Mdscsmentioning

confidence: 99%

“…The principal characteristic of MDSCs is their ability to suppress immune responses [6]. Consequently, and in the absence of specific markers for immunosuppressive MDSCs, a part of each MDSC sample should be tested in in vitro immunosuppression assays [45,50]. T-cells are the most documented target of MDSC-mediated immunosuppression.…”

Section: Immunosuppressive Mechanisms Of Mdscsmentioning

confidence: 99%

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MDSC in Mice and Men: Mechanisms of Immunosuppression in Cancer

Vanhaver

Bruggen

Bruger

2021

JCM

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Myeloid-derived suppressor cells (MDSCs) expand during pathological conditions in both humans and mice and their presence is linked to poor clinical outcomes for cancer patients. Studying MDSC immunosuppression is restricted by MDSCs’ rarity, short lifespan, heterogeneity, poor viability after freezing and the lack of MDSC-specific markers. In this review, we will compare identification and isolation strategies for human and murine MDSCs. We will also assess what direct and indirect immunosuppressive mechanisms have been attributed to MDSCs. While some immunosuppressive mechanisms are well-documented in mice, e.g., generation of ROS, direct evidence is still lacking in humans. In future, bulk or single-cell genomics could elucidate which phenotypic and functional phenotypes MDSCs adopt in particular microenvironments and help to identify potential targets for therapy.

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Section: Mdscs In Humansmentioning

confidence: 99%

Section: Common Challenges In Handling Murine and Human Mdscsmentioning

confidence: 99%

Section: Immunosuppressive Mechanisms Of Mdscsmentioning

confidence: 99%

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MDSC in Mice and Men: Mechanisms of Immunosuppression in Cancer

Vanhaver

Bruggen

Bruger

2021

JCM

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“…T cell suppression assay was performed as described previously (21,36). In brief, hGP100-restricted (B6.Cg-Thy1a/Cy TCRtransgenic) CD8 + T cells were isolated from PMEL-mice (32) using magnetic bead separation (Miltenyi Biotec) and labeled with Cell-Trace proliferation dye (Invitrogen.…”

Section: Suppression Of T Cell Proliferation Assaymentioning

confidence: 99%

TIGIT and PD-1 Immune Checkpoint Pathways Are Associated With Patient Outcome and Anti-Tumor Immunity in Glioblastoma

et al. 2021

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Glioblastoma (GBM) remains an aggressive brain tumor with a high rate of mortality. Immune checkpoint (IC) molecules are expressed on tumor infiltrating lymphocytes (TILs) and promote T cell exhaustion upon binding to IC ligands expressed by the tumor cells. Interfering with IC pathways with immunotherapy has promoted reactivation of anti-tumor immunity and led to success in several malignancies. However, IC inhibitors have achieved limited success in GBM patients, suggesting that other checkpoint molecules may be involved with suppressing TIL responses. Numerous IC pathways have been described, with current testing of inhibitors underway in multiple clinical trials. Identification of the most promising checkpoint pathways may be useful to guide the future trials for GBM. Here, we analyzed the The Cancer Genome Atlas (TCGA) transcriptomic database and identified PD1 and TIGIT as top putative targets for GBM immunotherapy. Additionally, dual blockade of PD1 and TIGIT improved survival and augmented CD8+ TIL accumulation and functions in a murine GBM model compared with either single agent alone. Furthermore, we demonstrated that this combination immunotherapy affected granulocytic/polymorphonuclear (PMN) myeloid derived suppressor cells (MDSCs) but not monocytic (Mo) MDSCs in in our murine gliomas. Importantly, we showed that suppressive myeloid cells express PD1, PD-L1, and TIGIT-ligands in human GBM tissue, and demonstrated that antigen specific T cell proliferation that is inhibited by immunosuppressive myeloid cells can be restored by TIGIT/PD1 blockade. Our data provide new insights into mechanisms of GBM αPD1/αTIGIT immunotherapy.

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“…[18][19][20] Figure 2 schematizes the current knowledge on the heterogeneity of neutrophils on the basis of their function and intrinsic density. In fact, besides the phenotype, one of the most often used criteria to distinguish neutrophil populations consists of defining their ability to exert either immunosuppressive actions (i.e., inhibition of the proliferation, or the production of IFN-γ, by activated T cells) 21 or to display enhanced proinflammatory functions [i.e., increased capacity to produce proinflammatory cytokines and/or to release neutrophil extracellular traps (NETs)]. 22 Cell density properties are uncovered by centrifuging blood or other biological samples over commercial gradients (for instance, Ficoll).…”

Section: Introductionmentioning

confidence: 99%

Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation

Tecchio

Cassatella

2020

Cell Mol Immunol

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Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a life-saving procedure used for the treatment of selected hematological malignancies, inborn errors of metabolism, and bone marrow failures. The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection. However, recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions. Accordingly, neutrophils are emerging as highly versatile cells that are able to acquire different, often opposite, functional capacities depending on the microenvironment and their differentiation status. Herein, we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT, from the hematopoietic stem cell (HSC) mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion. We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versus-host disease (GVHD) prophylaxis. Finally, the potential involvement of neutrophils in alloHSCT-related complications, such as transplant-associated thrombotic microangiopathy (TA-TMA), acute and chronic GVHD, and cytomegalovirus (CMV) reactivation, is also discussed. Based on the data reviewed herein, the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role. However, much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT.

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Protocol to assess the suppression of T-cell proliferation by human MDSC

Cited by 20 publications

References 18 publications

MDSC in Mice and Men: Mechanisms of Immunosuppression in Cancer

MDSC in Mice and Men: Mechanisms of Immunosuppression in Cancer

TIGIT and PD-1 Immune Checkpoint Pathways Are Associated With Patient Outcome and Anti-Tumor Immunity in Glioblastoma

Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation

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