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Disruption of CXCR2-Mediated MDSC Tumor Trafficking Enhances Anti-PD1 Efficacy
Open accessAbstract
Preventing trafficking of myeloid-derived suppressor cells to the tumor site enhances the efficiency of checkpoint blockade.
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“Notably, data from various mouse models indicate that disrupting the CXCR1/2–MDSC axis in tumours is therapeutically efficacious across a wide variety of solid cancers166–172.”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [168]
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Cites
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“…that proportion-based metrics may not directly index functional suppressive capacity, whereas surface molecules such as CD11b may better reflect adhesion/migration and recruitment programs that facilitate trafficking of suppressive myeloid cells to relevant tissues and promote immune escape [59].”
Self-citationCD55-expressing myeloid-derived suppressor cells (MDSCs) drive cancer immunoevasion
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“Other strategies include the C-C chemokine receptor 2 (CCR2) and C-X-C chemokine receptor 2 (CXCR2) which can possibly obstruct the entry of suppressive monocytes and granulocytic MDSCs into the tumours [72].”
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“…showing that CXCR1/2 inhibition to block neutrophil recruitment improves the efficacy of T cell checkpoint blockade in mice [ 99, 103, 105, 106, 108, 113 ], human cell-based organ-on-a-chip models could also be leveraged to evaluate combination immunotherapies targeting neutrophils and T cells…”
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“…of PMN-MDSCs — either through CXCR2 gene knockout or via small-molecule CXCR2 inhibitors — signi fi cantly improved outcomes in metastatic sarcoma models and enhanced the ef fi cacy of anti-PD-1 therapy against established tumors (155) (solid tumor evidence; relevance to MM remains to be con fi rmed).”
Li, X., Meng, Y., Dong, J., Ma, Y., Liu, D., Zhang, X., & Zhao, L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1941235
Ye, W., Zhong, L., Wang, X., & Chen, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1941227
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“The CXCL1/2–CXCR2 axis further sustains immunosuppression through MDSC accumulation and impaired CD8 ⁺ T-cell function [246–249] (Fig.”
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Peripheral immune tolerance as a driver of tumor immune escape and therapy resistance
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“Preclinical traf fi cking studies support testing these approaches (46, 47), but a fall in circulating neutrophils does not show that a suppressive tumor population has been removed.”
Liu, L., Guo, X., Dai, Y., Zhang, Q., Yang, J., Gu, R., Tang, M., Tan, M., & Nie, X. (2026) · Genes & Diseases · doi:10.1016/j.gendis.2026.102567
Metadata
- Authors
- Highfill, S. L., Cui, Y., Giles, A. J., Smith, J. P., Zhang, H., Morse, E., Kaplan, R. N., & Mackall, C. L.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Mackall, Crystal L.
- Venue
- Science Translational Medicine
- Published
- 2014-05-21
- Volume
- 6
- Issue
- 237
- Pages
- 237ra67-237ra67
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC6980372
- OpenAlex
- W2171524684
- Cited by
- 767
- References
- 50
- Citations by year
- 2026: 55 · 2025: 62 · 2024: 57 · 2023: 83 · 2022: 73 · 2021: 100 · 2020: 91 · 2019: 60 · 2018: 52 · 2017: 52 · 2016: 38 · 2015: 31 · 2014: 12
- FWCI
- 20.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (Z01BC011072, Z01BC010566, Z01SC010289)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- CXCR2, myeloid-derived suppressor cells, tumor immune evasion, anti-PD-1 therapy, rhabdomyosarcoma, pediatric sarcoma, interleukin-8, PD-L1, tumor immunosuppression
- MeSH terms
- Adolescent, Adult, Animals, Antibodies, Monoclonal, Antigens, Ly, Antineoplastic Combined Chemotherapy Protocols, Chemotaxis, Child, Child, Preschool, Female, Humans, Male, Mice, Inbred C57BL, Prognosis, Rhabdomyosarcoma, Time Factors, Neoplastic Stem Cells, Case-Control Studies, Cytokines, Interleukin-8, Mice, Knockout, Tumor Escape, Receptors, Interleukin-8B, CD11b Antigen, Cell Line, Tumor, Tumor Burden, Mice, Chemokine CXCL1, Young Adult, Tumor Microenvironment, B7-H1 Antigen
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