PMID- 11477558
OWN - NLM
STAT- MEDLINE
DCOM- 20010809
LR  - 20210102
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 93
IP  - 4
DP  - 2001 Aug 15
TI  - Efficient antitumor immunity derived from maturation of dendritic cells that had 
      phagocytosed apoptotic/necrotic tumor cells.
PG  - 539-48
AB  - Dendritic cells (DCs) that acquired antigen from apoptotic tumor cells are able 
      to induce major histocompatibility complex (MHC) class I-restricted cytotoxic T 
      lymphocytes and antitumor immunity. In the present study, we investigated the 
      efficiency of antitumor immunity derived from DCs that had phagocytosed 
      apoptotic/necrotic BL6-10 melanoma cells compared with that of DCs pulsed with 
      the tumor mTRP2 peptide. Our data showed that phagocytosis of apoptotic/necrotic 
      tumor cells resulted in maturation of DCs with up-regulated expression of 
      proinflammatory cytokines [interleukin (IL)-1beta, IL-6, tumor necrosis 
      factor-alpha, interferon-gamma and granulocyte-macrophage colony-stimulating 
      factor], chemokines (MIP-1alpha, MIP-1beta and MIP-2), the CC chemokine receptor 
      CCR7 and the cell surface molecules (MHC class II, CD11b, CD40 and CD86), and 
      down-regulated expression of the CC chemokine receptors CCR2 and CCR5. These 
      mature DCs displayed enhanced migration toward the CC chemokine MIP-3beta in a 
      chemotaxis assay in vitro and to the regional lymph nodes in an animal model in 
      vivo. Our data also showed that vaccination with DCs that had phagocytosed 
      apoptotic/necrotic BL6-10 cells was able to (i) more strongly stimulate 
      allogeneic T-cell proliferation in vitro, (ii) induce an in vivo Th1-type immune 
      response leading to more efficient tumor-specific cytotoxic CD8(+) 
      T-cell-mediated immunity and (iii) eradicate lung metastases in all 6 vaccinated 
      mice compared with mice vaccinated with DCs pulsed with the tumor mTRP2 peptide, 
      in which lung metastases were reduced (mean number of 16 per mouse) but not 
      completely eradicated. Therefore, DCs that had phagocytosed apoptotic/necrotic 
      tumor cells appear to offer new strategies in DC cancer vaccines.
CI  - Copyright 2001 Wiley-Liss, Inc.
FAU - Chen, Z
AU  - Chen Z
AD  - Saskatoon Cancer Center, Saskatoon, Saskatchewan, Canada.
FAU - Moyana, T
AU  - Moyana T
FAU - Saxena, A
AU  - Saxena A
FAU - Warrington, R
AU  - Warrington R
FAU - Jia, Z
AU  - Jia Z
FAU - Xiang, J
AU  - Xiang J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Ccr7 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, CCR7)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (Trp2 protein, vertebrate)
RN  - 0 (Trpc2 protein, mouse)
RN  - 207137-56-2 (Interleukin-4)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - 9LHU78OQFD (Lovastatin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/drug effects/immunology
MH  - Cancer Vaccines/*immunology
MH  - Cell Differentiation/drug effects/immunology
MH  - Cell Movement/physiology
MH  - Dendritic Cells/cytology/drug effects/*immunology
MH  - Female
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
MH  - Interleukin-4/pharmacology
MH  - Lovastatin/pharmacology
MH  - Lung Neoplasms/*immunology/pathology/secondary
MH  - Lymphocyte Activation/immunology
MH  - Melanoma, Experimental/*immunology/pathology/secondary
MH  - Membrane Proteins/pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Necrosis
MH  - Phagocytosis/immunology
MH  - Receptors, CCR7
MH  - Receptors, Chemokine/biosynthesis/physiology
MH  - T-Lymphocytes/immunology
MH  - TRPC Cation Channels
MH  - Tumor Cells, Cultured
EDAT- 2001/07/31 10:00
MHDA- 2001/08/10 10:01
CRDT- 2001/07/31 10:00
PHST- 2001/07/31 10:00 [pubmed]
PHST- 2001/08/10 10:01 [medline]
PHST- 2001/07/31 10:00 [entrez]
AID - 10.1002/ijc.1365 [pii]
AID - 10.1002/ijc.1365 [doi]
PST - ppublish
SO  - Int J Cancer. 2001 Aug 15;93(4):539-48. doi: 10.1002/ijc.1365.