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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.

Radice E, Bellone G, Miranda V - Transl Oncol (2015)

Bottom Line: Because of their potent immunoregulatory capacities, DCs have been exploited in anticancer vaccination, with limited success thus far.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgical Sciences, Corso Dogliotti 14, 10126 Turin, University of Turin, Italy. Electronic address: elisabetta.radice@unito.it.

No MeSH data available.


Related in: MedlinePlus

MoDCs sequentially stimulated with SKA-IL4 and SKA-IL-12 or rhIL-4 and rhIL-12 increased their capacity to initiate an allogenic response. MoDCs from colon carcinoma patients (n = 13, 6 nonmetastatic and 7 metastatic) or normal donors (n = 6) were generated from monocytes and exposed in the presence of predetermined concentrations of SKA-IL-4 (48 hours) and SKA-IL-12 (24 hours) as single agents or sequentially in parallel to the rh cytokines, and subjected to MLR with allogeneic naïve T cells in different MoDC-to-T cell ratios. MLR strength was measured by 3H-TdR incorporation of the co-culture. The plot shows the mean ± SE of 3H-TdR incorporation in cpm. Statistical significance versus control was determined using one-way ANOVA.*P < .05, **P < .01, and ***P < .001.
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f0015: MoDCs sequentially stimulated with SKA-IL4 and SKA-IL-12 or rhIL-4 and rhIL-12 increased their capacity to initiate an allogenic response. MoDCs from colon carcinoma patients (n = 13, 6 nonmetastatic and 7 metastatic) or normal donors (n = 6) were generated from monocytes and exposed in the presence of predetermined concentrations of SKA-IL-4 (48 hours) and SKA-IL-12 (24 hours) as single agents or sequentially in parallel to the rh cytokines, and subjected to MLR with allogeneic naïve T cells in different MoDC-to-T cell ratios. MLR strength was measured by 3H-TdR incorporation of the co-culture. The plot shows the mean ± SE of 3H-TdR incorporation in cpm. Statistical significance versus control was determined using one-way ANOVA.*P < .05, **P < .01, and ***P < .001.

Mentions: Figure 3 shows that, in colon carcinoma patients, following exposure to rhIL-4 or rhIL-12, MoDCs significantly increased their functional activity in comparison with untreated cells (P = .025 and P = .006, respectively). After sequential treatment with rhIL-4 (48 hours) and rhIL-12 (24 hours), MoDCs from tumor subjects became more potent MLR stimulatory cells than did untreated MoDCs (P < .001). By contrast, in MoDCs from patients, treatment with SKA cytokines alone did not significantly enhance their APC activity in MLR in comparison with untreated cells (SKA-IL-4: P = .172; SKA-IL-12: P = .178) even if, after sequential treatment with SKA-IL-4 (48 hours) and SKA-IL-12 (24 hours), MoDCs from tumor subjects became somewhat more potent MLR stimulatory cells than did untreated MoDCs, approaching statistical significance (P = .062).


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.

Radice E, Bellone G, Miranda V - Transl Oncol (2015)

MoDCs sequentially stimulated with SKA-IL4 and SKA-IL-12 or rhIL-4 and rhIL-12 increased their capacity to initiate an allogenic response. MoDCs from colon carcinoma patients (n = 13, 6 nonmetastatic and 7 metastatic) or normal donors (n = 6) were generated from monocytes and exposed in the presence of predetermined concentrations of SKA-IL-4 (48 hours) and SKA-IL-12 (24 hours) as single agents or sequentially in parallel to the rh cytokines, and subjected to MLR with allogeneic naïve T cells in different MoDC-to-T cell ratios. MLR strength was measured by 3H-TdR incorporation of the co-culture. The plot shows the mean ± SE of 3H-TdR incorporation in cpm. Statistical significance versus control was determined using one-way ANOVA.*P < .05, **P < .01, and ***P < .001.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4562983&req=5

f0015: MoDCs sequentially stimulated with SKA-IL4 and SKA-IL-12 or rhIL-4 and rhIL-12 increased their capacity to initiate an allogenic response. MoDCs from colon carcinoma patients (n = 13, 6 nonmetastatic and 7 metastatic) or normal donors (n = 6) were generated from monocytes and exposed in the presence of predetermined concentrations of SKA-IL-4 (48 hours) and SKA-IL-12 (24 hours) as single agents or sequentially in parallel to the rh cytokines, and subjected to MLR with allogeneic naïve T cells in different MoDC-to-T cell ratios. MLR strength was measured by 3H-TdR incorporation of the co-culture. The plot shows the mean ± SE of 3H-TdR incorporation in cpm. Statistical significance versus control was determined using one-way ANOVA.*P < .05, **P < .01, and ***P < .001.
Mentions: Figure 3 shows that, in colon carcinoma patients, following exposure to rhIL-4 or rhIL-12, MoDCs significantly increased their functional activity in comparison with untreated cells (P = .025 and P = .006, respectively). After sequential treatment with rhIL-4 (48 hours) and rhIL-12 (24 hours), MoDCs from tumor subjects became more potent MLR stimulatory cells than did untreated MoDCs (P < .001). By contrast, in MoDCs from patients, treatment with SKA cytokines alone did not significantly enhance their APC activity in MLR in comparison with untreated cells (SKA-IL-4: P = .172; SKA-IL-12: P = .178) even if, after sequential treatment with SKA-IL-4 (48 hours) and SKA-IL-12 (24 hours), MoDCs from tumor subjects became somewhat more potent MLR stimulatory cells than did untreated MoDCs, approaching statistical significance (P = .062).

Bottom Line: Because of their potent immunoregulatory capacities, DCs have been exploited in anticancer vaccination, with limited success thus far.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgical Sciences, Corso Dogliotti 14, 10126 Turin, University of Turin, Italy. Electronic address: elisabetta.radice@unito.it.

No MeSH data available.


Related in: MedlinePlus