Novel therapeutic strategies for treating esophageal adenocarcinoma: The potential of dendritic cell immunotherapy and combinatorial regimens

Milano, Francesca; Krishnadath, Kausilia K.

doi:10.1016/j.humimm.2008.07.006

Cited by 10 publications

(5 citation statements)

References 102 publications

(100 reference statements)

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“…It has been shown that an unfavorable tumor microenvironment, that inhibits the development and function of DCs and CTLs, plays a major role in this phenomenon (Zou, 2005, 2006). It has become clear that using DC-based therapeutic vaccines in combination with agents that modulate the tumor microenvironment, sensitize the tumor cells, or diminish the tumor bulk prior to DC treatment, would highly enhance the efficacy of this approach (Milano and Krishnadath, 2008; Kamrava et al, 2009; Dougan et al, 2010). Therefore, it is necessary to find new combinatorial approaches, which tilt the balance in favor of tumor immunity and enhance DC-induced T cell response in cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Nano-Curcumin Inhibits Proliferation of Esophageal Adenocarcinoma Cells and Enhances the T Cell Mediated Immune Response

Milano¹,

Mari²,

Luijtgaarden³

et al. 2013

Front. Oncol.

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In Western countries the incidence of the esophageal adenocarcinoma (EAC) has risen at a more rapid rate than that of any other malignancy. Despite intensive therapies this cancer is associated with extreme high morbidity and mortality. For this reason, novel effective therapeutic strategies are urgently required. Dendritic Cell (DC)-based immunotherapy is a promising novel treatment strategy, which combined with other anti-cancer strategies has been proven to be beneficial for cancer patients. Curcumin (diferuloylmethane), is a natural polyphenol that is known for its anti-cancer effects however, in it’s free form, curcumin has poor bioavailability. The aim of this study was to investigate whether using a highly absorptive form of curcumin, dispersed with colloidal nano-particles, named Theracurmin would be more effective against EAC cells and to analyze if this new compound affects DC-induced T cell response. As a result, we show efficient uptake of nano-curcumin by the EAC cell lines, OE33, and OE19. Moreover, nano-curcumin significantly decreased the proliferation of the EAC cells, while did not affect the normal esophageal cell line HET-1A. We also found that nano-curcumin significantly up-regulated the expression of the co-stimulatory molecule CD86 in DCs and significantly decreased the secretion of pro-inflammatory cytokines from in vitro activated T cells. When we combined T cells with nano-curcumin treatment in OE19 and OE33, we found that the basic levels of T cell induced cytotoxicity of 6.4 and 4.1%, increased to 15 and 13%, respectively. In conclusion, we found that nano-curcumin is effective against EAC, sensitizes EAC cells to T cell induced cytotoxicity and decreases the pro-inflammatory signals from T cells. Combining DC immunotherapy with nano-curcumin is potentially a promising approach for future treatment of EAC.

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Section: Introductionmentioning

confidence: 99%

Nano-Curcumin Inhibits Proliferation of Esophageal Adenocarcinoma Cells and Enhances the T Cell Mediated Immune Response

Milano¹,

Mari²,

Luijtgaarden³

et al. 2013

Front. Oncol.

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“…Indeed, MUC1 is highly expressed by several epithelial tumors, including breast, colon, kidney, lung, esophageal, stomach, and ovarian cancers. 67 Moreover, tumor-derived MUC1 has been shown to interact with differentiating monocytes and to inhibit mDC maturation and IL-12p70 secretion, while enhancing IL-10 secretion. 68 On the other hand, mDCs differentiated in the presence of PGE 2 also display a tolerogenic phenotype.…”

Section: Discussionmentioning

confidence: 99%

Dendritic Cells in Barrett's Esophagus Carcinogenesis

Somja

Demoulin

Roncarati

et al. 2013

The American Journal of Pathology

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Barrett's esophagus corresponds to the replacement of the normal esophageal squamous epithelium by a columnar epithelium through a metaplastic process. This tissue remodeling is associated with chronic gastroesophageal reflux and constitutes a premalignant lesion leading to a 30- to 60-fold increase in the risk to evolve into esophageal adenocarcinoma. The present study aimed to investigate a possible immune evasion in Barrett's esophagus favoring esophageal adenocarcinoma development. We demonstrated that myeloid and plasmacytoid dendritic cells are recruited during the esophageal metaplasia-dysplasia-carcinoma sequence, through the action of their chemoattractants, macrophage inflammatory protein 3α and chemerin. Next, we showed that, in contrast to plasmacytoid dendritic cells, myeloid dendritic cells, co-cultured with Barrett's esophagus and esophageal adenocarcinoma cell lines, display a tolerogenic phenotype. Accordingly, myeloid dendritic cells co-cultured with esophageal adenocarcinoma cell lines stimulated regulatory T cell differentiation from naïve CD4(+) T cells. In agreement with those results, we observed that both metaplastic areas and (pre)malignant lesions of the esophagus are infiltrated by regulatory T cells. In conclusion, soluble factors secreted by epithelial cells during the esophageal metaplasia-dysplasia-carcinoma sequence influence dendritic cell distribution and promote tumor progression by rendering them tolerogenic.

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“…Esophageal neoplasms is a common type of digestive tract neoplasms with high malignancy and poor prognosis. Five-year survival for malignant esophageal neoplasms is only about 13 ∼18%, even with advanced treatment ( Milano and Krishnadath (2008) ). The pathogenesis of esophageal tumors is diverse, and it is normally believed to be the result of environment-genetic-gene interaction.…”

Section: Case Studiesmentioning

confidence: 99%

Inferring human miRNA–disease associations via multiple kernel fusion on GCNII

Liang

et al. 2022

Front. Genet.

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Increasing evidence shows that the occurrence of human complex diseases is closely related to the mutation and abnormal expression of microRNAs(miRNAs). MiRNAs have complex and fine regulatory mechanisms, which makes it a promising target for drug discovery and disease diagnosis. Therefore, predicting the potential miRNA-disease associations has practical significance. In this paper, we proposed an miRNA–disease association predicting method based on multiple kernel fusion on Graph Convolutional Network via Initial residual and Identity mapping (GCNII), called MKFGCNII. Firstly, we built a heterogeneous network of miRNAs and diseases to extract multi-layer features via GCNII. Secondly, multiple kernel fusion method was applied to weight fusion of embeddings at each layer. Finally, Dual Laplacian Regularized Least Squares was used to predict new miRNA–disease associations by the combined kernel in miRNA and disease spaces. Compared with the other methods, MKFGCNII obtained the highest AUC value of 0.9631. Code is available at https://github.com/cuntjx/bioInfo.

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Novel therapeutic strategies for treating esophageal adenocarcinoma: The potential of dendritic cell immunotherapy and combinatorial regimens

Cited by 10 publications

References 102 publications

Nano-Curcumin Inhibits Proliferation of Esophageal Adenocarcinoma Cells and Enhances the T Cell Mediated Immune Response

Nano-Curcumin Inhibits Proliferation of Esophageal Adenocarcinoma Cells and Enhances the T Cell Mediated Immune Response

Dendritic Cells in Barrett's Esophagus Carcinogenesis

Inferring human miRNA–disease associations via multiple kernel fusion on GCNII

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