PMID- 20388795
OWN - NLM
STAT- MEDLINE
DCOM- 20100428
LR  - 20221207
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 70
IP  - 8
DP  - 2010 Apr 15
TI  - 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor 
      cells resulting in enhanced T cell-dependent antitumor immunity.
PG  - 3052-61
LID - 10.1158/0008-5472.CAN-09-3690 [doi]
AB  - Myeloid-derived suppressor cells (MDSC) accumulate in the spleen and tumor bed 
      during tumor growth. They contribute to the immune tolerance of cancer notably by 
      inhibiting the function of CD8(+) T cells. Thus, their elimination may hamper 
      tumor growth by enhancing antitumor T-cell functions. We have previously reported 
      that some anticancer agents relied on T cell-dependent anticancer responses to 
      achieve maximal efficacy. However, the effect of anticancer agents on MDSC has 
      remained largely unexplored. In this study, we observed that gemcitabine and 
      5-fluorouracil (5FU) were selectively cytotoxic on MDSC. In vivo, the treatment 
      of tumor-bearing mice with 5FU led to a major decrease in the number of MDSC in 
      the spleens and tumor beds of animals whereas no significant effect on T cells, 
      natural killer cells, dendritic cells, or B cells was noted. Interestingly, 5FU 
      showed a stronger efficacy over gemcitabine to deplete MDSC and selectively 
      induced MDSC apoptotic cell death in vitro and in vivo. The elimination of MDSC 
      by 5FU increased IFN-gamma production by tumor-specific CD8(+) T cells 
      infiltrating the tumor and promoted T cell-dependent antitumor responses in vivo. 
      Altogether, these findings suggest that the antitumor effect of 5FU is mediated, 
      at least in part, by its selective cytotoxic action on MDSC.
CI  - (c) 2010 AACR.
FAU - Vincent, Julie
AU  - Vincent J
AD  - INSERM Research Center 866, AVENIR Team, Faculty of Medicine, University of 
      Burgundy, Anti-Cancer Center, Georges Francois Leclerc, Dijon, France.
FAU - Mignot, Gregoire
AU  - Mignot G
FAU - Chalmin, Fanny
AU  - Chalmin F
FAU - Ladoire, Sylvain
AU  - Ladoire S
FAU - Bruchard, Melanie
AU  - Bruchard M
FAU - Chevriaux, Angelique
AU  - Chevriaux A
FAU - Martin, Francois
AU  - Martin F
FAU - Apetoh, Lionel
AU  - Apetoh L
FAU - Rebe, Cedric
AU  - Rebe C
FAU - Ghiringhelli, Francois
AU  - Ghiringhelli F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100413
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0W860991D6 (Deoxycytidine)
RN  - U3P01618RT (Fluorouracil)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Animals
MH  - Antimetabolites, Antineoplastic/*pharmacology
MH  - Apoptosis
MH  - CD8-Positive T-Lymphocytes/cytology
MH  - Cell Line, Tumor
MH  - Dendritic Cells/drug effects
MH  - Deoxycytidine/analogs & derivatives/pharmacology
MH  - Flow Cytometry
MH  - Fluorouracil/*pharmacology
MH  - Immune System
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Nude
MH  - Neoplasm Transplantation
MH  - T-Lymphocytes/*immunology/metabolism
MH  - Gemcitabine
EDAT- 2010/04/15 06:00
MHDA- 2010/04/29 06:00
CRDT- 2010/04/15 06:00
PHST- 2010/04/15 06:00 [entrez]
PHST- 2010/04/15 06:00 [pubmed]
PHST- 2010/04/29 06:00 [medline]
AID - 0008-5472.CAN-09-3690 [pii]
AID - 10.1158/0008-5472.CAN-09-3690 [doi]
PST - ppublish
SO  - Cancer Res. 2010 Apr 15;70(8):3052-61. doi: 10.1158/0008-5472.CAN-09-3690. Epub 
      2010 Apr 13.