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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 MoDC treatment with SKA-IL-4 and SKA- IL-12 alone or sequentially combined in priming Th1 response in comparison to rhIL-4 and rhIL-12. MLR was run by co-culturing untreated and SKA- or rh cytokine–treated MoDCs from normal subject (n = 5) and from nonmetastatic colon carcinoma patients (n = 6) (C and D) with naive allogeneic CD4+ T cells at stimulator (DCs)/responder (allogeneic naive allogeneic CD4+ T cells) ratio of 1:40. IL-12p70 and IFN-γ were measured in MLR supernatants by ELISA after 5 days of co-culture. Data are means ± SE pg/ml of duplicates. Statistical significance was determined using Mann-Whitney test. The P values are reported in the text.
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f0025: Effects of MoDC treatment with SKA-IL-4 and SKA- IL-12 alone or sequentially combined in priming Th1 response in comparison to rhIL-4 and rhIL-12. MLR was run by co-culturing untreated and SKA- or rh cytokine–treated MoDCs from normal subject (n = 5) and from nonmetastatic colon carcinoma patients (n = 6) (C and D) with naive allogeneic CD4+ T cells at stimulator (DCs)/responder (allogeneic naive allogeneic CD4+ T cells) ratio of 1:40. IL-12p70 and IFN-γ were measured in MLR supernatants by ELISA after 5 days of co-culture. Data are means ± SE pg/ml of duplicates. Statistical significance was determined using Mann-Whitney test. The P values are reported in the text.

Mentions: As shown in Figure 5, normal MoDCs (n = 5) cultured in MLR with naïve CD4+ T cells did not produce any or at most produced negligible levels of biologically active IL-12p70 (0.313 ± 0.183 pg/ml), whereas rhIL-4–, rhIL-12–, but especially rhIL-4/IL-12–treated MoDCs secreted IL-12p70 in the pg/ml range (47.89 ± 20.82 pg/ml, 61.63 ± 22.39 pg/ml, and 205.39 ± 71.64 pg/ml; P vs untreated MoDCs = .041, .024, and .021, respectively). MoDCs conditioned by SKA-IL-4 slightly increased, though not significantly, IL-12p70 production in the supernatant of MLR culture in comparison with the control (23.46 ± 14.79 pg/ml, P = .111). Conversely, MoDCs treated with SKA-IL-12 alone or sequentially combined SKA-IL-4/SKA-IL-12 enhanced IL-12p70 secretion (40.45 ± 14.85 pg/ml and 69.53 ± 23.59 pg/ml; P vs untreated MoDCs = .024 and .029, respectively), but less efficiently than the counterpart rh cytokine-exposed cells (p = 0.046, p = 0.025, 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 MoDC treatment with SKA-IL-4 and SKA- IL-12 alone or sequentially combined in priming Th1 response in comparison to rhIL-4 and rhIL-12. MLR was run by co-culturing untreated and SKA- or rh cytokine–treated MoDCs from normal subject (n = 5) and from nonmetastatic colon carcinoma patients (n = 6) (C and D) with naive allogeneic CD4+ T cells at stimulator (DCs)/responder (allogeneic naive allogeneic CD4+ T cells) ratio of 1:40. IL-12p70 and IFN-γ were measured in MLR supernatants by ELISA after 5 days of co-culture. Data are means ± SE pg/ml of duplicates. Statistical significance was determined using Mann-Whitney test. The P values are reported in the text.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0025: Effects of MoDC treatment with SKA-IL-4 and SKA- IL-12 alone or sequentially combined in priming Th1 response in comparison to rhIL-4 and rhIL-12. MLR was run by co-culturing untreated and SKA- or rh cytokine–treated MoDCs from normal subject (n = 5) and from nonmetastatic colon carcinoma patients (n = 6) (C and D) with naive allogeneic CD4+ T cells at stimulator (DCs)/responder (allogeneic naive allogeneic CD4+ T cells) ratio of 1:40. IL-12p70 and IFN-γ were measured in MLR supernatants by ELISA after 5 days of co-culture. Data are means ± SE pg/ml of duplicates. Statistical significance was determined using Mann-Whitney test. The P values are reported in the text.
Mentions: As shown in Figure 5, normal MoDCs (n = 5) cultured in MLR with naïve CD4+ T cells did not produce any or at most produced negligible levels of biologically active IL-12p70 (0.313 ± 0.183 pg/ml), whereas rhIL-4–, rhIL-12–, but especially rhIL-4/IL-12–treated MoDCs secreted IL-12p70 in the pg/ml range (47.89 ± 20.82 pg/ml, 61.63 ± 22.39 pg/ml, and 205.39 ± 71.64 pg/ml; P vs untreated MoDCs = .041, .024, and .021, respectively). MoDCs conditioned by SKA-IL-4 slightly increased, though not significantly, IL-12p70 production in the supernatant of MLR culture in comparison with the control (23.46 ± 14.79 pg/ml, P = .111). Conversely, MoDCs treated with SKA-IL-12 alone or sequentially combined SKA-IL-4/SKA-IL-12 enhanced IL-12p70 secretion (40.45 ± 14.85 pg/ml and 69.53 ± 23.59 pg/ml; P vs untreated MoDCs = .024 and .029, respectively), but less efficiently than the counterpart rh cytokine-exposed cells (p = 0.046, p = 0.025, 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