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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

Effect of low-dose SKA-IL-12 versus standard-dose rhIL-12 on the MoDC allostimulatory activity of colon carcinoma patients and healthy donors. MoDCs from nonmetastatic colon carcinoma patients (n = 6) and healthy donors (n = 5) were untreated (control) or 24-hour–treated with increasing concentrations of rhIL-12 or SKA-IL-12 and then co-cultured with allogenic CD4+ naïve cells (responders) at various stimulator-to-responder cell ratios in triplicate. Proliferative response was assessed by 3H-TdR uptake. Results are expressed as mean ± SE cpm. Statistical significance was determined using one-way ANOVA. *P < .05, *P < .05, and ***P = .001.
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f0010: Effect of low-dose SKA-IL-12 versus standard-dose rhIL-12 on the MoDC allostimulatory activity of colon carcinoma patients and healthy donors. MoDCs from nonmetastatic colon carcinoma patients (n = 6) and healthy donors (n = 5) were untreated (control) or 24-hour–treated with increasing concentrations of rhIL-12 or SKA-IL-12 and then co-cultured with allogenic CD4+ naïve cells (responders) at various stimulator-to-responder cell ratios in triplicate. Proliferative response was assessed by 3H-TdR uptake. Results are expressed as mean ± SE cpm. Statistical significance was determined using one-way ANOVA. *P < .05, *P < .05, and ***P = .001.

Mentions: The efficacy of 24-hour treatment with increasing concentrations of SKA-IL-12 (0.25, 0.5, 1, and 2 fg/ml) or with the standard dose of rh-IL-12 (1 ng/ml) on allostimulatory activity of CD14+-derived DCs from nonmetastatic colon carcinoma patients (n = 6) and healthy donors (n = 5) was evaluated preliminarily by the MLR assay. As shown in Figure 2A, when MoDCs were pretreated with rhIL-12 (1 ng/ml) before functional assay, the allostimulatory activity increased significantly in nonmetastatic colon carcinoma patients (P = .026), although there was a high variation in interindividual response; none of the concentrations of SKA-IL-12 used affected APC capacity. In contrast, in healthy donors, the highest concentration of SKA-IL-12 evaluated (2 fg/ml) significantly increased the allostimulatory activity of MoDCs in comparison with untreated MoDCs (P = .034) even if the effect of the standard dose of rhIL-12 was more marked (P = .001). These results suggest that MoDCs from nonmetastatic colon carcinoma patients were functionally poorly responsive or unresponsive to low-dose SKA-IL-12–mediated stimulation; this is presumably because of a defective expression of IL-12R complex, which nevertheless is sufficient for pharmacological doses of IL-12 to induce partial correction of MoDC allostimulatory activity.


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)

Effect of low-dose SKA-IL-12 versus standard-dose rhIL-12 on the MoDC allostimulatory activity of colon carcinoma patients and healthy donors. MoDCs from nonmetastatic colon carcinoma patients (n = 6) and healthy donors (n = 5) were untreated (control) or 24-hour–treated with increasing concentrations of rhIL-12 or SKA-IL-12 and then co-cultured with allogenic CD4+ naïve cells (responders) at various stimulator-to-responder cell ratios in triplicate. Proliferative response was assessed by 3H-TdR uptake. Results are expressed as mean ± SE cpm. Statistical significance was determined using one-way ANOVA. *P < .05, *P < .05, and ***P = .001.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0010: Effect of low-dose SKA-IL-12 versus standard-dose rhIL-12 on the MoDC allostimulatory activity of colon carcinoma patients and healthy donors. MoDCs from nonmetastatic colon carcinoma patients (n = 6) and healthy donors (n = 5) were untreated (control) or 24-hour–treated with increasing concentrations of rhIL-12 or SKA-IL-12 and then co-cultured with allogenic CD4+ naïve cells (responders) at various stimulator-to-responder cell ratios in triplicate. Proliferative response was assessed by 3H-TdR uptake. Results are expressed as mean ± SE cpm. Statistical significance was determined using one-way ANOVA. *P < .05, *P < .05, and ***P = .001.
Mentions: The efficacy of 24-hour treatment with increasing concentrations of SKA-IL-12 (0.25, 0.5, 1, and 2 fg/ml) or with the standard dose of rh-IL-12 (1 ng/ml) on allostimulatory activity of CD14+-derived DCs from nonmetastatic colon carcinoma patients (n = 6) and healthy donors (n = 5) was evaluated preliminarily by the MLR assay. As shown in Figure 2A, when MoDCs were pretreated with rhIL-12 (1 ng/ml) before functional assay, the allostimulatory activity increased significantly in nonmetastatic colon carcinoma patients (P = .026), although there was a high variation in interindividual response; none of the concentrations of SKA-IL-12 used affected APC capacity. In contrast, in healthy donors, the highest concentration of SKA-IL-12 evaluated (2 fg/ml) significantly increased the allostimulatory activity of MoDCs in comparison with untreated MoDCs (P = .034) even if the effect of the standard dose of rhIL-12 was more marked (P = .001). These results suggest that MoDCs from nonmetastatic colon carcinoma patients were functionally poorly responsive or unresponsive to low-dose SKA-IL-12–mediated stimulation; this is presumably because of a defective expression of IL-12R complex, which nevertheless is sufficient for pharmacological doses of IL-12 to induce partial correction of MoDC allostimulatory activity.

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