Dendritic cell biology and cancer therapy

Kim

J of Cellular Biochemistry

et al. 2006

We investigated whether phosphatidic acid (PA) can differentiate the promyelocytic leukemia (PML)-retinoic acid receptor a (RARa)-expressing acute promyelocytic leukemic cell line, NB4, to dendritic cell (DC)-like cells. Dioctanoyl-PA alone upregulated the expression of DC markers. The expression of DC markers on NB4 cells was potentiated by the overexpression of phospholipase D and upregulation was blocked by the addition of n-butanol, an inhibitor of PA production. The expression of CD11c, CD83, and CCR7 in PA-treated NB4 cells was further increased by tumor necrosis factor (TNF)-a treatment. Increased functional capacities were also found in PA-differentiated and TNF-aactivated NB4 cells with respect to changes in T-cell proliferation, cytokine production, endocytic activity, and cytolytic capacity against undifferentiated NB4 cells. PA alone increased the phosphorylation of extracellular signal-regulated kinase (ERK)-1/2. The expression of DC markers was downregulated by PD98059, a specific inhibitor of ERK kinase or transient transfection of mutant-ERK. The level of PML-RARa fusion protein was decreased by PA treatment and PD98059 blocked the decrease of PML-RARa. These results suggest that PA induces differentiation of NB4 cells into DC-like cells and that the upregulation of antigen presenting cell markers is mediated by the activation of ERK and the downregulation of PML-RARa levels.

Section: Enhancement Of DC Marker Expression Bymentioning

confidence: 96%

Phosphatidic acid induces the differentiation of human acute promyelocytic leukemic cells into dendritic cell‐like

Kim

J of Cellular Biochemistry

et al. 2006

Am J Respir Crit Care Med

“…Furthermore, NTM causes primary infections in patients with no history of respiratory illness (31)(32)(33)(34)(35), and what is of greater concern is the increasing frequency of infection in recent years (30,31,35,36) in these patients. Therefore, it is important to find an efficient treatment that succeeds in the cure of mycobacterial infections, with shorter periods of treatment and lower systemic drug dosage.…”

Section: Discussionmentioning

confidence: 99%

Targeted Delivery of Amikacin into Granuloma

Montes-Worboys¹,

Brown²,

Regev³

et al. 2010

Rationale: Nontuberculous mycobacterial (NTM) infection is a growing problem in the United States and remains underrecognized in the developing world. The management of NTM infections is further complicated by several factors, including the need to use high systemic doses of toxic agents, the length of therapy, and the development of drug resistance. Objectives: We have evaluated the use of monocyte-derived dendritic cells (DCs) as a delivery vehicle for a luminescent derivative of amikacin prepared by conjugation to fluorescein isothiocyanate (FITC) (amikacin-FITC) into granulomas formed in the tissues of mice infected with Mycobacterium avium. Methods: Amikacin-FITC was prepared and quantitative fluorescence was used to track the intracellular uptake of this modified antibiotic. The antibiotic activity of amikacin-FITC was also determined to be comparable to unmodified amikacin against M. avium. Amikacin-FITC-loaded DCs were first primed with M. avium, and then the cells were injected into the tail vein of infected mice. After 24 hours, the mice were sacrificed and the tissues were analyzed under fluorescence microscope. Measurements and Main Results: We found that we were able to deliver amikacin into granulomas in a mouse model of disseminated mycobacterial infection. No increase in levels of monocyte chemoattractant protein-1 and its CCR2 as markers of inflammation were found when DCs were treated with amikacin-FITC. Conclusions: DC-based drug delivery may be an adjunct and useful method of delivering high local concentrations of antibiotics into mycobacterial granulomas.

“…DCs are the most potent APCs mediating the effective in vitro and in vivo immune responses [20,21]. These cells are used for antigen-specific immunotherapy of cancer because they are the most efficient APCs that can induce primary immune responses [22,23].…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy with tumor cell lysate-pulsed CD8α+ dendritic cells modulates intra-tumor and spleen lymphocyte subpopulations

Azadmehr

Aa²,

Amirghofran³

et al. 2013

neo

Using cellular adjuvants including dendritic cells (DCs) has provided a promising approach in immunotherapy of cancer. Our previous study showed that mice immunization with tumor cell lysate-pulsed DCs (TL-CD8α+DCs) could significantly suppress the tumor growth and increase mice survival. The aim of the present study was to investigate the impact of TL-CD8α+DC vaccine on intra-tumor and spleen lymphocyte subpopulations in tumor-bearing mice. A Balb/c mouse model of fibrosarcoma was used and changes in various lymphocyte subpopulations including CD4 + , CD8+ and CD4T cells in mice immunized with TL-CD8α + DCs were studied. The cytotoxic activity of the lymphocytes and tumor growth inhibitory rate were also measured. Immunotherapy with TL-CD8α + DCs significantly enhanced both CD4+ and CD8+ lymphocytes, whereas decreased CD4 + CD25 + Foxp3 + regulatory T cells as well as the tumor growth rate. There was also a decrease in the ratio of regulatory T cells to CD4 + and to CD8 + lymphocytes in both the tumor and spleen tissues as compared to that in the non-immunized control mice. Immunization with TL-CD8α + DCs as well as CD8α + DCs significantly increased the splenocytes cytotoxic activity by 45.1% and 18.2% of control, respectively. In conclusion, the current study indicated that TL-CD8α + DCs can enhance tumor immunity against the fibrosarcoma by enhancing both the CD4 + and CD8 + lymphocytes and reducing regulatory T cells. This finding suggests the usefulness of TL-CD8α + DCs vaccine for cancer treatment.