Myeloid-derived suppressor cells (MDSCs) are cells of neutrophil and monocyte lineages with potent immunosuppressive activity. Numerous studies in mice and humans have identified important roles for MDSCs in suppressing the antitumour response and determining the efficacy of cancer immunotherapies. However, there is still much controversy regarding their identity, ontogeny and functions that must be resolved to fulfill their therapeutic potential. In this Viewpoint, Nature Reviews Immunology invites eight experts in the field to share their thoughts on the key questions and challenges in MDSC research.
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Leila Akkari’s laboratory is interested in understanding the complex interactions between cancer and stromal cells within tumours to determine how both cell-autonomous and non-autonomous signals regulate primary cancer malignancies in brain and liver tumours, in order to harness myeloid cells in personalized anticancer treatments. Leila is an associate member of the Netherlands Cancer Institute, an EMBO Young Investigator, ERC grantee and member of the Oncode Institute.
Ido Amit’s laboratory pioneered the development of single-cell genomics technologies and their application to the characterization of the immune system. His work has identified many immune cell states and has greatly impacted discoveries in both basic immunology and its translation towards the development of immunotherapies.
Vincenzo Bronte is professor of immunology in the Department of Medicine of Verona University and scientific director of the Instituto Oncologico Veneto in Padua, Italy. His research group focuses on immune-evasive strategies of cancer, with particular attention to myeloid-dependent alterations and pancreatic tumours. He contributed to the initial identification and characterization of MDSCs.
Zvi G. Fridlender is a physician-scientist, head of the Department of Internal Medicine D and the Laboratory of Lung Cancer at Hadassah-Hebrew University Medical Center, Jerusalem. He has authored more than 100 publications mostly on the role and diversity of neutrophils in cancer and other diseases.
Florent Ginhoux is a laboratory director in Gustave Roussy focusing on the role of myeloid cells in tumour progression and on paediatric cancers. He is also an adjunct professor at the Singapore Immunology Network (SIgN) A*STAR, the Shanghai Immunology Institute, Jiao Tong University, and in the Translational Immunology Institute, SingHealth and Duke NUS, Singapore.
Dmitry I. Gabrilovich is an executive director and chief scientist in cancer immunology at AstraZeneca, where he performs discovery and translational studies focusing on myeloid cells. He is an ACS research professor. He was a pioneer in the discovery and characterization of MDSCs and the development of MDSC-targeting strategies.
Catherine C. ‘Lynn’ Hedrick is the Georgia Research Alliance Bradley-Turner Eminent Scholar in Cancer and Vascular Immunology at the Medical College of Georgia, USA. She is a founding director of the Immunology Center of Georgia and Head of the Cancer Immunology, Inflammation, and Tolerance (CIIT) Division of the Georgia Cancer Center. Research efforts in her laboratory focus on human monocyte functions in health, cancer and cardiovascular disease.
Suzanne Ostrand-Rosenberg’s laboratory demonstrated that CD4+ T helper cells are required for the efficacy of therapeutic cancer vaccines but that efficacy is limited by tumour-induced immune suppression. The laboratory’s discovery of MDSCs, and of chronic inflammation as the driver of MDSCs, linked the immune system with cancer progression and identified MDSCs as crucial cells obstructing cancer immunotherapies.
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I.A. is an advisor to Immunai. D.I.G. is an employee and shareholder of AstraZeneca. Z.G.F. is a co-founder and CMO of ImmunyX, focused on neutrophil modulation in disease; and on the scientific advisory board of TigaTx, which is developing an IgA therapeutic monoclonal antibody platform for solid tumours. The other authors declare no competing interests.
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Akkari, L., Amit, I., Bronte, V. et al. Defining myeloid-derived suppressor cells. Nat Rev Immunol (2024). https://doi.org/10.1038/s41577-024-01062-0
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DOI: https://doi.org/10.1038/s41577-024-01062-0
