Therapeutic targeting of tumour myeloid cells
Open accessAbstract
Myeloid cells are pivotal within the immunosuppressive tumour microenvironment. The accumulation of tumour-modified myeloid cells derived from monocytes or neutrophils - termed 'myeloid-derived suppressor cells' - and tumour-associated macrophages is associated with poor outcome and resistance to treatments such as chemotherapy and immune checkpoint inhibitors. Unfortunately, there has been little success in large-scale clinical trials of myeloid cell modulators, and only a few distinct strategies have been used to target suppressive myeloid cells clinically so far. Preclinical and translational studies have now elucidated specific functions for different myeloid cell subpopulations within the tumour microenvironment, revealing context-specific roles of different myeloid cell populations in disease progression and influencing response to therapy. To improve the success of myeloid cell-targeted therapies, it will be important to target tumour types and patient subsets in which myeloid cells represent the dominant driver of therapy resistance, as well as to determine the most efficacious treatment regimens and combination partners. This Review discusses what we can learn from work with the first generation of myeloid modulators and highlights recent developments in modelling context-specific roles for different myeloid cell subtypes, which can ultimately inform how to drive more successful clinical trials.
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Accumulation and activation of immunosuppressive myeloid cells are strongly correlated with reduced efficacy of immunotherapies and poor prognosis across various cancers.
“Their accumulation and activation are strongly correlated with reduced efficacy of immunotherapies and poor prognosis across various cancers, such as colorectal cancer, pancreatic cancer, glioblastoma, breast cancer, liver cancer, head and neck cancer, lung cancer, and prostate cancer13.”
From Oligomeric cystatin C supports the immunosuppressive activity of myeloid cells through interaction with inhibitory receptors (2025) · cites this paper as [13]
The available passages (Dosing Strategy > M-MDSC; page not given) list myeloid-cell markers and treatment trials in several cancers, but do not link myeloid-cell accumulation or activation to immunotherapy efficacy or prognosis. Searches for “poor prognosis,” “immunotherapy resistance,” and the named cancer types did not find a passage establishing the claimed correlation. (LLM, conf=0.72)
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- Authors
- Barry, S. T., Gabrilovich, D. I., Sansom, O. J., Campbell, A. D., & Morton, J. P.
- Affiliations
- AstraZeneca (United Kingdom) (GB)
- AstraZeneca (United States) (US)
- Cancer Research UK Scotland Institute (GB)
- Corresponding author
- Barry, Simon T.
- Venue
- Nature Reviews Cancer
- Published
- 2023-02-06
- Volume
- 23
- Issue
- 4
- Pages
- 216-237
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- OpenAlex
- W4319298155
- Cited by
- 305
- References
- 27
- Citations by year
- 2026: 71 · 2025: 104 · 2024: 96 · 2023: 34
- FWCI
- 8.48
- Type
- journal article
- Language
- en
- Open access
- green
- eprints.gla.ac.uk
- Licence
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion, cc-by-sa)
- Funders
- Cancer Research UK (DRCQQR-May21\100002, 29996, 25233)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- myeloid-derived suppressor cells, tumour-associated macrophages, tumor microenvironment, immunosuppression, treatment resistance, chemoresistance, immune checkpoint inhibitors, clinical trial design
- MeSH terms
- Myeloid-Derived Suppressor Cells, Humans, Immunotherapy, Neoplasms, Neutrophils, Myeloid Cells, Tumor Microenvironment
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