PMID- 12888337
OWN - NLM
STAT- MEDLINE
DCOM- 20030923
LR  - 20190817
IS  - 0022-4804 (Print)
IS  - 0022-4804 (Linking)
VI  - 112
IP  - 2
DP  - 2003 Jun 15
TI  - In vitro induction of tumor-specific HLA class I-restricted CD8+ cytotoxic T 
      lymphocytes from patients with locally advanced breast cancer by tumor 
      antigen-pulsed autologous dendritic cells.
PG  - 189-97
AB  - BACKGROUND: Early dissemination of treatment-resistant tumor cells remains the 
      major cause of metastatic recurrence and death in breast cancer patients. 
      Dendritic cells (DCs) are the most powerful antigen-presenting cells, and 
      recently DC-based vaccination has shown great promise for the treatment of human 
      malignancies by immunological intervention. MATERIALS AND METHODS: CD8+ T 
      lymphocytes derived from peripheral blood mononuclear cells stimulated in vitro 
      with autologous breast tumor antigen-pulsed DCs were tested for their ability to 
      induce a HLA class I restricted cytotoxic T lymphocyte (CTL) response against 
      autologous tumor cells. To correlate cytotoxic activity by CTL with T cell 
      phenotype, two-color flow cytometric analysis of surface markers and 
      intracellular cytokine expression was performed. RESULTS: DC pulsed with breast 
      tumor extracts consistently elicited a tumor-specific HLA class I restricted CTL 
      response in vitro in three consecutive patients harboring locally advanced breast 
      cancer. CTL expressed strong cytolytic activity against autologous tumor cells 
      but did not lyse autologous Epstein Barr virus-transformed lymphoblastoid cell 
      lines and showed variable cytotoxicity against the natural killer-sensitive cell 
      line K-562. In all patients, two color flow cytometric analysis of surface 
      markers and intracellular cytokine expression demonstrated that tumor-specific 
      CTL exhibited an heterogeneous CD8+/CD56+ expression and a striking Th1 cytokine 
      bias (IFNgamma(high)/IL-4 (low)). CONCLUSIONS: Tumor lysate-pulsed DCs can 
      consistently stimulate specific CD8+ CTLs able to kill autologous tumor cells in 
      patients with locally advanced breast cancer in vitro. Tumor antigen-pulsed 
      DC-based vaccinations may be appropriate for the treatment of residual and/or 
      chemotherapy-resistant breast cancer refractory to standard salvage treatment 
      modalities.
FAU - Kass, Rena
AU  - Kass R
AD  - Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, 
      AR 72205, USA.
FAU - Agha, Jamshed
AU  - Agha J
FAU - Bellone, Stefania
AU  - Bellone S
FAU - Palmieri, Michela
AU  - Palmieri M
FAU - Cane, Stefania
AU  - Cane S
FAU - Bignotti, Eliana
AU  - Bignotti E
FAU - Henry-Tillman, Rhonda
AU  - Henry-Tillman R
FAU - Hutchins, Laura
AU  - Hutchins L
FAU - Cannon, Martin J
AU  - Cannon MJ
FAU - Klimberg, Suzanne
AU  - Klimberg S
FAU - Santin, Alessandro D
AU  - Santin AD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (Antigens, Neoplasm)
SB  - IM
MH  - Adenocarcinoma/*immunology
MH  - Adult
MH  - Aged
MH  - Antigens, Neoplasm/immunology
MH  - Breast Neoplasms/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Dendritic Cells/*immunology
MH  - Female
MH  - Genes, MHC Class I/*immunology/physiology
MH  - Humans
MH  - Middle Aged
MH  - Tumor Cells, Cultured
EDAT- 2003/07/31 05:00
MHDA- 2003/09/25 05:00
CRDT- 2003/07/31 05:00
PHST- 2003/07/31 05:00 [pubmed]
PHST- 2003/09/25 05:00 [medline]
PHST- 2003/07/31 05:00 [entrez]
AID - S0022480403001471 [pii]
AID - 10.1016/s0022-4804(03)00147-1 [doi]
PST - ppublish
SO  - J Surg Res. 2003 Jun 15;112(2):189-97. doi: 10.1016/s0022-4804(03)00147-1.