PMID- 26310379
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150828
LR  - 20201001
IS  - 1936-5233 (Print)
IS  - 1936-5233 (Electronic)
IS  - 1936-5233 (Linking)
VI  - 8
IP  - 4
DP  - 2015 Aug
TI  - Enhancement of the Immunostimulatory Functions of Ex Vivo-Generated Dendritic 
      Cells from Early-Stage Colon Cancer Patients by Consecutive Exposure to Low Doses 
      of Sequential-Kinetic-Activated IL-4 and IL-12. A Preliminary Study.
PG  - 327-38
LID - S1936-5233(15)00055-8 [pii]
LID - 10.1016/j.tranon.2015.06.005 [doi]
AB  - Dendritic cells (DCs), specialized antigen-presenting cells bridging innate and 
      adaptive immunity, play a crucial role in determining specific immune response to 
      tumors. Because of their potent immunoregulatory capacities, DCs have been 
      exploited in anticancer vaccination, with limited success thus far. This pilot 
      study compared low-dose interleukin (IL)-4 and IL-12 prepared by sequential 
      kinetic activation (SKA) with standard doses of the same recombinant human 
      cytokines on functional activity of ex vivo-generated monocyte-derived (Mo) DCs 
      from colon carcinoma patients and normal subjects. MoDCs were exposed to medium 
      alone, SKA-IL-4 (0.5 fg/ml), or SKA-IL-12 (2 fg/ml), alone or consecutively 
      combined, in parallel with rhIL-4 (50 ng/ml) and rhIL-12 (1 ng/ml). Primary 
      allogeneic one-way mixed lymphocyte reaction (MLR) was the end point to assess in 
      vitro T-lymphocyte proliferation in response to MoDCs, and secreted IL-12p70 and 
      interferon-gamma in MLR supernatants measured by ELISA to assay for T-helper 
      1-promoting MoDC phenotype. No single agent enhanced the compromised 
      allostimulatory activity of MoDCs from colon cancer patients, unlike healthy 
      donors. However, MoDCs from nonmetastatic colon cancer patients, after sequential 
      exposure to SKA-IL-4 (48 hours) and SKA-IL-12 (24 hours), displayed increased 
      T-cell stimulatory capacity by MLR and acquired driving T-helper 1 polarization 
      activity, although less markedly than the effects induced by recombinant human 
      cytokines or found in normal subjects. These results point to an immunomodulatory 
      capacity of low-dose SKA-IL-4 and SKA-IL-12 and encourage further investigation 
      to provide clues for the rational development of new and more effective 
      immunotherapeutic strategies against cancer.
CI  - Copyright (c) 2015 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Radice, Elisabetta
AU  - Radice E
AD  - Department of Surgical Sciences, Corso Dogliotti 14, 10126 Turin, University of 
      Turin, Italy. Electronic address: elisabetta.radice@unito.it.
FAU - Bellone, Graziella
AU  - Bellone G
AD  - Department of Medical Sciences, Via Genova 3, 10126 Turin, University of Turin, 
      Italy. Electronic address: graziella.bellone@unito.it.
FAU - Miranda, Vincenzo
AU  - Miranda V
AD  - Clinical Research Unit, GUNA S.p.a., Via Palmanova, 71, 20132 Milan, Italy. 
      Electronic address: v.miranda@guna.it.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Transl Oncol
JT  - Translational oncology
JID - 101472619
PMC - PMC4562983
EDAT- 2015/08/28 06:00
MHDA- 2015/08/28 06:01
PMCR- 2015/08/24
CRDT- 2015/08/28 06:00
PHST- 2015/04/15 00:00 [received]
PHST- 2015/06/09 00:00 [revised]
PHST- 2015/06/23 00:00 [accepted]
PHST- 2015/08/28 06:00 [entrez]
PHST- 2015/08/28 06:00 [pubmed]
PHST- 2015/08/28 06:01 [medline]
PHST- 2015/08/24 00:00 [pmc-release]
AID - S1936-5233(15)00055-8 [pii]
AID - 10.1016/j.tranon.2015.06.005 [doi]
PST - ppublish
SO  - Transl Oncol. 2015 Aug;8(4):327-38. doi: 10.1016/j.tranon.2015.06.005.