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Cited by 158Immune cells in cancerImmunotherapy and Immune ResponsesCancer, Stress, Anesthesia, and Immune Response

Paclitaxel promotes differentiation of myeloid-derived suppressor cells into dendritic cells in vitro in a TLR4-independent manner

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Michels, Tillmann, Shurin, Galina V., Naiditch, Hiam, Sevko, Alexandra, Umansky, Viktor, Shurin, Michael R.·2012·Journal of Immunotoxicology
DOI 10.3109/1547691x.2011.642418PMC PMC3386478
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Abstract

Myeloid cells play a key role in the outcome of anti-tumor immunity and response to anti-cancer therapy, since in the tumor microenvironment they may exert both stimulatory and inhibitory pressures on the proliferative, angiogenic, metastatic, and immunomodulating potential of tumor cells. Therefore, understanding the mechanisms of myeloid regulatory cell differentiation is critical for developing strategies for the therapeutic reversal of myeloid derived suppressor cell (MDSC) accumulation in the tumor-bearing hosts. Here, using an in vitro model system, several potential mechanisms of the direct effect of paclitaxel on MDSC were tested, which might be responsible for the anti-tumor potential of low-dose paclitaxel therapy in mice. It was hypothesized that a decreased level of MDSC in vivo after paclitaxel administration might be due to (i) the blockage of MDSC generation, (ii) an induction of MDSC apoptosis, or (iii) the stimulation of MDSC differentiation. The results revealed that paclitaxel in ultra-low concentrations neither increased MDSC apoptosis nor blocked MDSC generation, but stimulated MDSC differentiation towards dendritic cells. This effect of paclitaxel was TLR4-independent since it was not diminished in cell cultures originated from TLR4-/- mice. These results support a new concept that certain chemotherapeutic agents in ultra-low non-cytotoxic doses may suppress tumor progression by targeting several cell populations in the tumor microenvironment, including MDSC.

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Authors
Michels, T., Shurin, G. V., Naiditch, H., Sevko, A., Umansky, V., & Shurin, M. R.
Affiliations
  • German Cancer Research Center (DE)
  • University of Pittsburgh (US)
  • University of Pittsburgh Medical Center (US)
Corresponding author
Shurin, Michael R.
ORCID
Venue
Journal of Immunotoxicology
Publisher
Informa UK Limited
Published
2012-01-28
Volume
9
Issue
3
Pages
292-300
ISSN
  • 1547-6901 (ISSN-L)
  • 1547-691X
DOI
10.3109/1547691x.2011.642418
PMC
PMC3386478
OpenAlex
W1983906625
Cited by
158
References
4
Citations by year
2026: 6 · 2025: 8 · 2024: 15 · 2023: 11 · 2022: 13 · 2021: 18 · 2020: 15 · 2019: 6 · 2018: 8 · 2017: 8 · 2016: 9 · 2015: 8 · 2014: 14 · 2013: 13 · 2012: 6
FWCI
5.73
Type
journal article
Language
en
Open access
Locations
  • Journal of Immunotoxicology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Deutsches Krebsforschungszentrum
  • National Institutes of Health
  • National Cancer Institute (R01CA154369)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
Keywords
paclitaxel, myeloid-derived suppressor cells, dendritic cell differentiation, TLR4-independent signaling, tumor microenvironment, low-dose chemotherapy, antitumor immunity, anticancer agents
MeSH terms
Animals, Antineoplastic Agents, Phytogenic, Cell Differentiation, Dendritic Cells, Male, Neoplasms, Paclitaxel, Myeloid Cells, Cell Line, Tumor, Toll-Like Receptor 4, Mice, Tumor Microenvironment

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