PMID- 20702612
OWN - NLM
STAT- MEDLINE
DCOM- 20110202
LR  - 20220410
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 16
IP  - 18
DP  - 2010 Sep 15
TI  - A novel chemoimmunomodulating property of docetaxel: suppression of 
      myeloid-derived suppressor cells in tumor bearers.
PG  - 4583-94
LID - 10.1158/1078-0432.CCR-10-0733 [doi]
AB  - PURPOSE: Myeloid-derived suppressor cells (MDSC) accumulate in tumor-bearing 
      hosts and are associated with immune suppression. To date, there have only been 
      few studies that evaluate the direct effect of chemotherapeutic agents on MDSCs. 
      Agents that inhibit MDSCs may be useful in the treatment of patients with various 
      cancers. EXPERIMENTAL DESIGN: We investigated the in vivo effects of docetaxel on 
      immune function in 4T1-Neu mammary tumor-bearing mice to examine if a favorable 
      immunomodulatory effect accompanies tumor suppression. Primary focus was on the 
      differentiation status of MDSCs and their ability to modulate T-cell responses. 
      RESULTS: Docetaxel administration significantly inhibited tumor growth in 4T1-Neu 
      tumor-bearing mice and considerably decreased MDSC proportion in the spleen. The 
      treatment also selectively increased CTL responses. Docetaxel-pretreated MDSCs 
      cocultured with OT-II splenocytes in the presence of OVA(323-339) showed 
      OT-II-specific CD4 activation and expansion in vitro. In characterizing the 
      phenotype of MDSCs for M1 (CCR7) and M2 [mannose receptor (CD206)] markers, MDSCs 
      from untreated tumor bearers were primarily MR(+) with few CCR7(+) cells. 
      Docetaxel treatment polarized MDSCs toward an M1-like phenotype, resulting in 40% 
      of MDSCs expressing CCR7 in vivo and in vitro, and macrophage differentiation 
      markers such as MHC class II, CD11c, and CD86 were upregulated. Interestingly, 
      docetaxel induced cell death selectively in MR(+) MDSCs while sparing the M1-like 
      phenotype. Finally, inhibition of signal transducer and activator of 
      transcription 3 may in part be responsible for the observed results. CONCLUSIONS: 
      These findings suggest potential clinical benefit for the addition of docetaxel 
      to current immunotherapeutic protocols.
CI  - (c)2010 AACR.
FAU - Kodumudi, Krithika N
AU  - Kodumudi KN
AD  - Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, Florida 33612, 
      USA.
FAU - Woan, Karrune
AU  - Woan K
FAU - Gilvary, Danielle L
AU  - Gilvary DL
FAU - Sahakian, Eva
AU  - Sahakian E
FAU - Wei, Sheng
AU  - Wei S
FAU - Djeu, Julie Y
AU  - Djeu JY
LA  - eng
GR  - T32 CA115308/CA/NCI NIH HHS/United States
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100811
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Taxoids)
RN  - 15H5577CQD (Docetaxel)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology/therapeutic use
MH  - Cell Differentiation/drug effects/immunology
MH  - Cell Line, Tumor
MH  - Cytotoxicity, Immunologic/drug effects
MH  - Docetaxel
MH  - Female
MH  - Immune Tolerance/immunology
MH  - Immunomodulation/*drug effects
MH  - Immunosuppressive Agents/pharmacology/therapeutic use
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Transgenic
MH  - Myeloid Cells/*drug effects/immunology/physiology
MH  - Neoplasm Transplantation
MH  - Neoplasms/drug therapy/*immunology
MH  - T-Lymphocytes/*drug effects/immunology
MH  - Taxoids/*pharmacology/therapeutic use
PMC - PMC3874864
MID - NIHMS539161
COIS- Disclosure of Potential Conflicts of Interest No potential conflicts of interest 
      were disclosed.
EDAT- 2010/08/13 06:00
MHDA- 2011/02/03 06:00
PMCR- 2013/12/30
CRDT- 2010/08/13 06:00
PHST- 2010/08/13 06:00 [entrez]
PHST- 2010/08/13 06:00 [pubmed]
PHST- 2011/02/03 06:00 [medline]
PHST- 2013/12/30 00:00 [pmc-release]
AID - 1078-0432.CCR-10-0733 [pii]
AID - 10.1158/1078-0432.CCR-10-0733 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2010 Sep 15;16(18):4583-94. doi: 10.1158/1078-0432.CCR-10-0733. 
      Epub 2010 Aug 11.