Skip to main content
Top
Published in: Cancer Immunology, Immunotherapy 4/2019

01-04-2019 | Symposium-in-Writing Paper

How to measure the immunosuppressive activity of MDSC: assays, problems and potential solutions

Authors: Annika M. Bruger, Anca Dorhoi, Gunes Esendagli, Katarzyna Barczyk-Kahlert, Pierre van der Bruggen, Marie Lipoldova, Tomas Perecko, Juan Santibanez, Margarida Saraiva, Jo A. Van Ginderachter, Sven Brandau

Published in: Cancer Immunology, Immunotherapy | Issue 4/2019

Login to get access

Abstract

Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of mononuclear and polymorphonuclear myeloid cells, which are present at very low numbers in healthy subjects, but can expand substantially under disease conditions. Depending on disease type and stage, MDSC comprise varying amounts of immature and mature differentiation stages of myeloid cells. Validated unique phenotypic markers for MDSC are still lacking. Therefore, the functional analysis of these cells is of central importance for their identification and characterization. Various disease-promoting and immunosuppressive functions of MDSC are reported in the literature. Among those, the capacity to modulate the activity of T cells is by far the most often used and best-established read-out system. In this review, we critically evaluate the assays available for the functional analysis of human and murine MDSC under in vitro and in vivo conditions. We also discuss critical issues and controls associated with those assays. We aim at providing suggestions and recommendations useful for the contemporary biological characterization of MDSC.
Literature
2.
go back to reference Libby P (2007) Inflammatory mechanisms: the molecular basis of inflammation and disease. Nutr Rev 65:S140-6CrossRefPubMed Libby P (2007) Inflammatory mechanisms: the molecular basis of inflammation and disease. Nutr Rev 65:S140-6CrossRefPubMed
12.
go back to reference Raber PL, Thevenot P, Sierra R, Wyczechowska D, Halle D, Ramirez ME, Ochoa AC, Fletcher M, Velasco C, Wilk A, Reiss K, Rodriguez PC (2014) Subpopulations of myeloid-derived suppressor cells impair T cell responses through independent nitric oxide-related pathways. Int J Cancer 134:2853–2864. https://doi.org/10.1002/ijc.28622 CrossRefPubMed Raber PL, Thevenot P, Sierra R, Wyczechowska D, Halle D, Ramirez ME, Ochoa AC, Fletcher M, Velasco C, Wilk A, Reiss K, Rodriguez PC (2014) Subpopulations of myeloid-derived suppressor cells impair T cell responses through independent nitric oxide-related pathways. Int J Cancer 134:2853–2864. https://​doi.​org/​10.​1002/​ijc.​28622 CrossRefPubMed
16.
go back to reference Li H, Han Y, Guo Q, Zhang M, Cao X (2009) Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1. J Immunol 182:240–249CrossRefPubMed Li H, Han Y, Guo Q, Zhang M, Cao X (2009) Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1. J Immunol 182:240–249CrossRefPubMed
19.
go back to reference Kusmartsev S, Nefedova Y, Yoder D, Gabrilovich DI (2004) Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol 172:989–999CrossRefPubMed Kusmartsev S, Nefedova Y, Yoder D, Gabrilovich DI (2004) Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol 172:989–999CrossRefPubMed
21.
go back to reference Youn J-I, Nagaraj S, Collazo M, Gabrilovich DI (2008) Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol 181:5791–5802CrossRefPubMed Youn J-I, Nagaraj S, Collazo M, Gabrilovich DI (2008) Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol 181:5791–5802CrossRefPubMed
26.
go back to reference Carretero-Iglesia L, Bouchet-Delbos L, Louvet C, Drujont L, Segovia M, Merieau E, Chiffoleau E, Josien R, Hill M, Cuturi M-C, Moreau A (2016) Comparative study of the immunoregulatory capacity of in vitro generated tolerogenic dendritic cells, suppressor macrophages, and myeloid-derived suppressor cells. Transplantation 100:2079–2089. https://doi.org/10.1097/TP.0000000000001315 CrossRefPubMed Carretero-Iglesia L, Bouchet-Delbos L, Louvet C, Drujont L, Segovia M, Merieau E, Chiffoleau E, Josien R, Hill M, Cuturi M-C, Moreau A (2016) Comparative study of the immunoregulatory capacity of in vitro generated tolerogenic dendritic cells, suppressor macrophages, and myeloid-derived suppressor cells. Transplantation 100:2079–2089. https://​doi.​org/​10.​1097/​TP.​0000000000001315​ CrossRefPubMed
29.
go back to reference Bronte V, Wang M, Overwijk WW, Surman DR, Pericle F, Rosenberg SA, Restifo NP (1998) Apoptotic death of CD8+ T lymphocytes after immunization: induction of a suppressive population of Mac-1+/Gr-1+ cells. J Immunol 161:5313–5320PubMed Bronte V, Wang M, Overwijk WW, Surman DR, Pericle F, Rosenberg SA, Restifo NP (1998) Apoptotic death of CD8+ T lymphocytes after immunization: induction of a suppressive population of Mac-1+/Gr-1+ cells. J Immunol 161:5313–5320PubMed
40.
go back to reference Brandau S, Trellakis S, Bruderek K, Schmaltz D, Steller G, Elian M, Suttmann H, Schenck M, Welling J, Zabel P, Lang S (2011) Myeloid-derived suppressor cells in the peripheral blood of cancer patients contain a subset of immature neutrophils with impaired migratory properties. J Leukoc Biol 89:311–317. https://doi.org/10.1189/jlb.0310162 CrossRefPubMed Brandau S, Trellakis S, Bruderek K, Schmaltz D, Steller G, Elian M, Suttmann H, Schenck M, Welling J, Zabel P, Lang S (2011) Myeloid-derived suppressor cells in the peripheral blood of cancer patients contain a subset of immature neutrophils with impaired migratory properties. J Leukoc Biol 89:311–317. https://​doi.​org/​10.​1189/​jlb.​0310162 CrossRefPubMed
47.
go back to reference Kusmartsev S, Nagaraj S, Gabrilovich DI (2005) Tumor-associated CD8+ T cell tolerance induced by bone marrow-derived immature myeloid cells. J Immunol 175:4583–4592CrossRefPubMed Kusmartsev S, Nagaraj S, Gabrilovich DI (2005) Tumor-associated CD8+ T cell tolerance induced by bone marrow-derived immature myeloid cells. J Immunol 175:4583–4592CrossRefPubMed
51.
go back to reference Liu C-Y, Wang Y-M, Wang C-L, Feng P-H, Ko H-W, Liu Y-H, Wu Y-C, Chu Y, Chung F-T, Kuo C-H, Lee K-Y, Lin S-M, Lin H-C, Wang C-H, Yu C-T, Kuo H-P (2010) Population alterations of l-arginase- and inducible nitric oxide synthase-expressed CD11b+/CD14−/CD15+/CD33+ myeloid-derived suppressor cells and CD8+ T lymphocytes in patients with advanced-stage non-small cell lung cancer. J Cancer Res Clin Oncol 136:35–45. https://doi.org/10.1007/s00432-009-0634-0 CrossRefPubMed Liu C-Y, Wang Y-M, Wang C-L, Feng P-H, Ko H-W, Liu Y-H, Wu Y-C, Chu Y, Chung F-T, Kuo C-H, Lee K-Y, Lin S-M, Lin H-C, Wang C-H, Yu C-T, Kuo H-P (2010) Population alterations of l-arginase- and inducible nitric oxide synthase-expressed CD11b+/CD14−/CD15+/CD33+ myeloid-derived suppressor cells and CD8+ T lymphocytes in patients with advanced-stage non-small cell lung cancer. J Cancer Res Clin Oncol 136:35–45. https://​doi.​org/​10.​1007/​s00432-009-0634-0 CrossRefPubMed
53.
go back to reference Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A, Mellor AL (1999) Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med 189:1363–1372CrossRefPubMedPubMedCentral Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A, Mellor AL (1999) Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med 189:1363–1372CrossRefPubMedPubMedCentral
61.
go back to reference Eisenblaetter M, Flores-Borja F, Lee JJ, Wefers C, Smith H, Hueting R, Cooper MS, Blower PJ, Patel D, Rodriguez-Justo M, Milewicz H, Vogl T, Roth J, Tutt A, Schaeffter T, Ng T (2017) Visualization of tumor-immune interaction—target-specific imaging of S100A8/A9 reveals pre-metastatic niche establishment. Theranostics 7:2392–2401. https://doi.org/10.7150/thno.17138 CrossRefPubMedPubMedCentral Eisenblaetter M, Flores-Borja F, Lee JJ, Wefers C, Smith H, Hueting R, Cooper MS, Blower PJ, Patel D, Rodriguez-Justo M, Milewicz H, Vogl T, Roth J, Tutt A, Schaeffter T, Ng T (2017) Visualization of tumor-immune interaction—target-specific imaging of S100A8/A9 reveals pre-metastatic niche establishment. Theranostics 7:2392–2401. https://​doi.​org/​10.​7150/​thno.​17138 CrossRefPubMedPubMedCentral
63.
go back to reference Condamine T, Dominguez GA, Youn J-I, Kossenkov AV, Mony S, Alicea-Torres K, Tcyganov E, Hashimoto A, Nefedova Y, Lin C, Partlova S, Garfall A, Vogl DT, Xu X, Knight SC, Malietzis G, Lee GH, Eruslanov E, Albelda SM et al (2016) Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients. Sci Immunol 1:aaf8943. https://doi.org/10.1126/sciimmunol.aaf8943 CrossRefPubMedPubMedCentral Condamine T, Dominguez GA, Youn J-I, Kossenkov AV, Mony S, Alicea-Torres K, Tcyganov E, Hashimoto A, Nefedova Y, Lin C, Partlova S, Garfall A, Vogl DT, Xu X, Knight SC, Malietzis G, Lee GH, Eruslanov E, Albelda SM et al (2016) Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients. Sci Immunol 1:aaf8943. https://​doi.​org/​10.​1126/​sciimmunol.​aaf8943 CrossRefPubMedPubMedCentral
64.
66.
Metadata
Title
How to measure the immunosuppressive activity of MDSC: assays, problems and potential solutions
Authors
Annika M. Bruger
Anca Dorhoi
Gunes Esendagli
Katarzyna Barczyk-Kahlert
Pierre van der Bruggen
Marie Lipoldova
Tomas Perecko
Juan Santibanez
Margarida Saraiva
Jo A. Van Ginderachter
Sven Brandau
Publication date
01-04-2019
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 4/2019
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-018-2170-8

Other articles of this Issue 4/2019

Cancer Immunology, Immunotherapy 4/2019 Go to the issue

ACKNOWLEDGEMENT TO REVIEWERS

Acknowledgements

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine