PMID- 19041139
OWN - NLM
STAT- MEDLINE
DCOM- 20090511
LR  - 20211020
IS  - 0161-5890 (Print)
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 46
IP  - 5
DP  - 2009 Feb
TI  - Dysfunctional DC subsets in RCC patients: ex vivo correction to yield an 
      effective anti-cancer vaccine.
PG  - 893-901
LID - 10.1016/j.molimm.2008.09.015 [doi]
AB  - Dendritic cells (DCs) are potent antigen-presenting cells responsible for the 
      activation and functional polarization of specific T cells. In patients with 
      renal cell carcinoma (RCC) and other cancers, coordinate DC and T cell defects 
      have been reported. In particular, DC and T cell functional subsets that are not 
      conducive to tumor clearance are hypothesized to predominate in patients with 
      advanced-stage disease. Two major peripheral blood DC subsets have been 
      identified in humans: myeloid dendritic cells (mDCs) and plasmacytoid dendritic 
      cells (pDCs) that are believed to mediate contrasting effects on cancer immunity. 
      Given the lack of information regarding DC subsets in patients with RCC, in the 
      present study we have investigated the comparative frequencies and activation 
      states of mDC and pDC in peripheral blood, cancer tissues and lymph nodes of 
      patients with RCC using flow cytometry and immunohistochemistry. Three monoclonal 
      antibodies (mAbs) reactive against specific DC subsets (BDCA-2 or BDCA-4 for pDC 
      and BDCA-1 and BDCA-3 which represent two distinct subsets of mDC, mDC1 and mDC2, 
      respectively) were employed. We observed a significant reduction of both DC 
      subsets in the peripheral blood of patients as compared to normal donors. 
      Similarly, both mDC and pDC were recruited in large numbers into RCC tumor 
      tissues, where they displayed an immature phenotype (DC-LAMP(-)) and appeared 
      unable to differentiate into mature DC (CD83(+)) that were competent to migrate 
      to draining lymph nodes. However, we were readily able to generate ex vivo mDC 
      from RCC patients. These DC stimulated robust anti-tumor CTL in vitro and would 
      be envisioned for use in DC-based vaccines applied in patients with RCC whose 
      existing immune system is judged dysfunctional, anergic or prone to undergo 
      apoptosis.
FAU - Gigante, M
AU  - Gigante M
AD  - Bioagromed, University of Foggia, via Napoli, 71100 Foggia, Italy.
FAU - Blasi, A
AU  - Blasi A
FAU - Loverre, A
AU  - Loverre A
FAU - Mancini, V
AU  - Mancini V
FAU - Battaglia, M
AU  - Battaglia M
FAU - Selvaggi, F P
AU  - Selvaggi FP
FAU - Maiorano, E
AU  - Maiorano E
FAU - Napoli, A
AU  - Napoli A
FAU - Castellano, G
AU  - Castellano G
FAU - Storkus, W J
AU  - Storkus WJ
FAU - Gesualdo, L
AU  - Gesualdo L
FAU - Ranieri, E
AU  - Ranieri E
LA  - eng
GR  - R01 CA057840/CA/NCI NIH HHS/United States
GR  - UL1 TR000005/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081128
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Cancer Vaccines)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Apoptosis/immunology
MH  - Cancer Vaccines/*immunology
MH  - Carcinoma, Renal Cell/*immunology/pathology/therapy
MH  - Clonal Anergy/immunology
MH  - Dendritic Cells/*immunology/pathology
MH  - Female
MH  - Humans
MH  - Kidney Neoplasms/*immunology/pathology/therapy
MH  - Male
MH  - Middle Aged
MH  - Myeloid Cells/*immunology/pathology
MH  - Plasma Cells/*immunology/pathology
MH  - T-Lymphocytes/immunology/pathology
PMC - PMC3427923
MID - NIHMS399856
EDAT- 2008/12/02 09:00
MHDA- 2009/05/12 09:00
PMCR- 2012/08/27
CRDT- 2008/12/02 09:00
PHST- 2008/07/24 00:00 [received]
PHST- 2008/09/08 00:00 [accepted]
PHST- 2008/12/02 09:00 [pubmed]
PHST- 2009/05/12 09:00 [medline]
PHST- 2008/12/02 09:00 [entrez]
PHST- 2012/08/27 00:00 [pmc-release]
AID - S0161-5890(08)00666-4 [pii]
AID - 10.1016/j.molimm.2008.09.015 [doi]
PST - ppublish
SO  - Mol Immunol. 2009 Feb;46(5):893-901. doi: 10.1016/j.molimm.2008.09.015. Epub 2008 
      Nov 28.