PMID- 11196166
OWN - NLM
STAT- MEDLINE
DCOM- 20010201
LR  - 20210103
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 61
IP  - 1
DP  - 2001 Jan 1
TI  - Local administration of dendritic cells inhibits established breast tumor growth: 
      implications for apoptosis-inducing agents.
PG  - 228-36
AB  - Dendritic cells (DCs) can efficiently acquire foreign antigen(s) from apoptotic 
      cells and induce MHC class I-restricted, antigen-specific CTLs. An accumulation 
      of DCs within solid tumor masses in situ has been associated indirectly with a 
      more favorable prognosis. Therefore, DCs may offer an efficient means for 
      triggering immune responses within tumors, particularly in those masses 
      containing significant apoptosis. We examined whether delivery of DCs could, 
      alone, impact on the progressive growth of a tumor with a relatively high 
      apoptotic index. We detected significant early apoptosis within the mass of a 
      s.c. growing murine MT-901 breast carcinoma. DCs could efficiently engulf MT-901 
      tumor apoptotic cells in vitro. Intratumoral injections of syngeneic but not 
      allogeneic DCs resulted in significant inhibition of MT-901 tumor growth. 
      Histological examination of the tumor revealed intense mononuclear cell 
      infiltration during and after DC injections. Tumor growth inhibition was 
      relatively radiosensitive and dependent on host-derived CD8+ T cells. The 
      baseline level of tumor apoptosis could be increased substantially by tumor 
      necrosis factor alpha administration, leading to a greater DC-mediated antitumor 
      effect. The antitumor effect could also be enhanced by first pulsing DCs with the 
      foreign helper protein, keyhole limpet hemocyanin, prior to intratumoral delivery 
      and combining it with the systemic administration of interleukin 2. Splenocytes 
      from treated animals showed heightened levels of specific CTL activity and 
      production of cytokines. The level of in situ tumor apoptosis appears to play a 
      critical role in DC-mediated antitumor effects. The potential implication of 
      these findings in DC-based tumor therapy strategies is discussed.
FAU - Candido, K A
AU  - Candido KA
AD  - The Medical School, University of Michigan Medical Center, Ann Arbor 48103, USA.
FAU - Shimizu, K
AU  - Shimizu K
FAU - McLaughlin, J C
AU  - McLaughlin JC
FAU - Kunkel, R
AU  - Kunkel R
FAU - Fuller, J A
AU  - Fuller JA
FAU - Redman, B G
AU  - Redman BG
FAU - Thomas, E K
AU  - Thomas EK
FAU - Nickoloff, B J
AU  - Nickoloff BJ
FAU - Mule, J J
AU  - Mule JJ
LA  - eng
GR  - 1 R01CA71669/CA/NCI NIH HHS/United States
GR  - 1 R01CA87019/CA/NCI NIH HHS/United States
GR  - 5 P01 CA59327/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antigens)
RN  - 0 (Interleukin-2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9013-72-3 (Hemocyanins)
RN  - FV4Y0JO2CX (keyhole-limpet hemocyanin)
SB  - IM
MH  - Animals
MH  - Antigens/immunology/pharmacology
MH  - Apoptosis/*drug effects/*immunology
MH  - Cell Division/drug effects/immunology
MH  - Dendritic Cells/drug effects/*immunology
MH  - Female
MH  - Hemocyanins/immunology/pharmacology
MH  - *Immunotherapy, Adoptive
MH  - Injections, Intralesional
MH  - Interleukin-2/pharmacology
MH  - Mammary Neoplasms, Experimental/*immunology/*pathology/therapy
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neoplasm Transplantation
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/immunology/pharmacology
EDAT- 2001/02/24 12:00
MHDA- 2001/02/28 10:01
CRDT- 2001/02/24 12:00
PHST- 2001/02/24 12:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2001/02/24 12:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2001 Jan 1;61(1):228-36.