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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

Effects of standard-dose rhIL-4 and/or rhIL-12 and low-dose SKA-IL-4 and/or SKA-IL-12 on APC activity in MLR of MoDCs from nonmetastatic colon carcinoma patients (n = 6) and from metastatic colon carcinoma patients (n = 7). MoDCs were untreated or pretreated with 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. The figure shows the mean percentages ± SE of 3H-TdR incorporation in cpm. Statistical significance was determined using one-way ANOVA.Rh/SKA cytokine pretreated nonmetastatic/metastatic colon carcinoma MoDCs versus untreated nonmetastatic/metastatic colon carcinoma MoDCs: *P < .05 and **P < .01.Nonmetastatic colon carcinoma MoDCs versus metastatic colon carcinoma MoDCs: ●●P < .01 and ●●●P < .0001.
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f0020: Effects of standard-dose rhIL-4 and/or rhIL-12 and low-dose SKA-IL-4 and/or SKA-IL-12 on APC activity in MLR of MoDCs from nonmetastatic colon carcinoma patients (n = 6) and from metastatic colon carcinoma patients (n = 7). MoDCs were untreated or pretreated with 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. The figure shows the mean percentages ± SE of 3H-TdR incorporation in cpm. Statistical significance was determined using one-way ANOVA.Rh/SKA cytokine pretreated nonmetastatic/metastatic colon carcinoma MoDCs versus untreated nonmetastatic/metastatic colon carcinoma MoDCs: *P < .05 and **P < .01.Nonmetastatic colon carcinoma MoDCs versus metastatic colon carcinoma MoDCs: ●●P < .01 and ●●●P < .0001.

Mentions: When patients were subdivided into two groups based on disease stage (Figure 4), significant increases in APC activity in MLR of rhIL-4, rhIL-12, or rhIL-4 and rhIL-12 sequentially combined pretreated MoDCs from early-stage colon carcinoma patients (n = 6, Dukes’ A and B) were observed in comparison with untreated cells (P = .034, P = .002, and P = .019, respectively). By contrast, antigen-presenting activity of MoDCs from colon carcinoma patients with metastatic lymph nodes (n = 7, Dukes’ C) was enhanced only after exposure to rhIL-4 followed by rhIL-12 (P = .011). Moreover, MLR response levels in the presence of MoDCs pretreated with rhIL-4 and rhIL-12 as single agents, or with rhIL-4 and rhIL-12 in subsequent association, were significantly lower in colon carcinoma patients with metastatic lymph nodes than in those with locally extended tumors (Dukes’ A + B, n = 6) (P = .003, P = .006, P = .004, and P = .023, respectively).


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)

Effects of standard-dose rhIL-4 and/or rhIL-12 and low-dose SKA-IL-4 and/or SKA-IL-12 on APC activity in MLR of MoDCs from nonmetastatic colon carcinoma patients (n = 6) and from metastatic colon carcinoma patients (n = 7). MoDCs were untreated or pretreated with 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. The figure shows the mean percentages ± SE of 3H-TdR incorporation in cpm. Statistical significance was determined using one-way ANOVA.Rh/SKA cytokine pretreated nonmetastatic/metastatic colon carcinoma MoDCs versus untreated nonmetastatic/metastatic colon carcinoma MoDCs: *P < .05 and **P < .01.Nonmetastatic colon carcinoma MoDCs versus metastatic colon carcinoma MoDCs: ●●P < .01 and ●●●P < .0001.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0020: Effects of standard-dose rhIL-4 and/or rhIL-12 and low-dose SKA-IL-4 and/or SKA-IL-12 on APC activity in MLR of MoDCs from nonmetastatic colon carcinoma patients (n = 6) and from metastatic colon carcinoma patients (n = 7). MoDCs were untreated or pretreated with 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. The figure shows the mean percentages ± SE of 3H-TdR incorporation in cpm. Statistical significance was determined using one-way ANOVA.Rh/SKA cytokine pretreated nonmetastatic/metastatic colon carcinoma MoDCs versus untreated nonmetastatic/metastatic colon carcinoma MoDCs: *P < .05 and **P < .01.Nonmetastatic colon carcinoma MoDCs versus metastatic colon carcinoma MoDCs: ●●P < .01 and ●●●P < .0001.
Mentions: When patients were subdivided into two groups based on disease stage (Figure 4), significant increases in APC activity in MLR of rhIL-4, rhIL-12, or rhIL-4 and rhIL-12 sequentially combined pretreated MoDCs from early-stage colon carcinoma patients (n = 6, Dukes’ A and B) were observed in comparison with untreated cells (P = .034, P = .002, and P = .019, respectively). By contrast, antigen-presenting activity of MoDCs from colon carcinoma patients with metastatic lymph nodes (n = 7, Dukes’ C) was enhanced only after exposure to rhIL-4 followed by rhIL-12 (P = .011). Moreover, MLR response levels in the presence of MoDCs pretreated with rhIL-4 and rhIL-12 as single agents, or with rhIL-4 and rhIL-12 in subsequent association, were significantly lower in colon carcinoma patients with metastatic lymph nodes than in those with locally extended tumors (Dukes’ A + B, n = 6) (P = .003, P = .006, P = .004, and P = .023, respectively).

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