This study is designed to present an agent-based model (ABM) to simulate the interactions between... more This study is designed to present an agent-based model (ABM) to simulate the interactions between tumor cells and the immune system in the melanoma model. The Myeloid-derived Suppressor Cells (MDSCs) and dendritic cells (DCs) are considered in this model as immunosuppressive and antigen-presenting agents respectively.The animal experiment was performed on 68 B16F10 melanoma tumor-bearing C57BL/6 female mice to collect dynamic data for ABM implementation and validation. Animals were divided into 4 groups; group 1 was control (no treatment) while groups 2 and 3 were treated with DC vaccine and low-dose 5- fluorouracil (5-FU) respectively and group 4 was treated with both DC Vaccine and low-dose of 5-FU. The tumor growth rate, number of MDSC, and presence of CD8+/CD107a+ T cells in the tumor microenvironment were evaluated in each group. Firstly, the tumor cells, the effector immune cells, DCs, and the MDSCs have been considered as the agents of the ABM model and their interaction meth...
Additional file 1. Table S1. Examples of Discrepancies between the Original English Version and B... more Additional file 1. Table S1. Examples of Discrepancies between the Original English Version and Back-translated English Version.
Background: The 4T1 cells tumor growth and metastatic pattern in BALB/c mice very closely mimic h... more Background: The 4T1 cells tumor growth and metastatic pattern in BALB/c mice very closely mimic human breast cancer. These herbal remedies used in traditional folk medicine have been the source of many medically beneficial drugs. The aim of the current study was to evaluate the anti-proliferative activity of the asafoetida, ginseng and fennel ethanolic extracts on mouse breast cancer 4T1 cell-line invitro.Method: in this experimental study, Asafoetida, gensing and fennel were extracted; 4T1 mouse mammary tumor cell line were cultured in 48-well flat bottom plate in density of 50x103 per well in 100 µl RPMI1640 medium then different dilutions of each extract (25 , 50, 100, 200, 500, and 2000 μg/ml) were added to cell culture. Cells then were incubated at 37 oC for 24 hours. After 24 h, cell Proliferation was determined by the BRDU assay . dataset of experiments were collected and analysed with SPSS19 software. Significant level of Data was Examined with one-way ANOVA method and P
The goal of this study is introducing a quantified feature for investigating the quality manner a... more The goal of this study is introducing a quantified feature for investigating the quality manner and interaction between the immune system and tumor cell. For this purpose, we introduced an agent based model which uses two agents, consists tumor cell and CD8+ cells and the environment which consists IL-2 and TGF- β cytokines. This model works using a variety of ratios. The most important ratio of this model is the tumor’s proliferation ratio. We investigated this ratio in three states of tumor-immune system interaction consist elimination, equilibrium and escape using a raw model, then this ratio investigated using models which optimized by experimental data. The results showed that, if model be leaning to the elimination state, this ratio falls faster and if be leaning to the escape state, this ratio will reduce slowly. This result proved by models which used experimental data for optimizing. Therefore, using this ratio we can compare the different manner of tumor-immune system inte...
BACKGROUND Melanoma progression and metastasis is suggested to be mediated by increased accumulat... more BACKGROUND Melanoma progression and metastasis is suggested to be mediated by increased accumulation of myeloid derived suppressor cells. Various chemotherapeutic drugs such as 5-Fluorouracil in single low concentration have the capacity, at least in part, to reverse tumor progression by reducing myeloid derived suppressor cells-mediated immunosuppression. OBJECTIVE To assess whether multiple low doses of 5-fluorouracil could repress myeloid derived suppressor cells in low frequency and, in turn, could enhance anti-tumor responses and promote a more prolonged survival in a murine melanoma model. METHODS Fifty milligram per kilogram body weight dose of 5-Flourouracil was administered intraperitoneally 4 times with 3-day intervals to C57BL/6 mice after B16 melanoma tumor models were established. The frequency and suppressive functions of myeloid derived suppressor cells and induction of anti-tumor CD8+ T cells as well as tumor growth and survival were evaluated in drug treated and unt...
Otosclerosis is a common cause of conductive hearing loss. It is surgically treated with stapedec... more Otosclerosis is a common cause of conductive hearing loss. It is surgically treated with stapedectomy or stapedotomy. Sensory- neural hearing loss is an uncommon but known complication of this surgery. A 25-year-old Iranian female patient with bilateral otosclerosis underwent right stapedotomy and developed bilateral sensorineural hearing loss a few days after the surgery which recovered with appropriate treatment. The possible causes and their clinical courses are discussed in this study. Sensorineural hearing loss after stapedotomy has many different etiologies. Generally, causes which are not directly related to the surgery should also be considered.
Background The purpose of this study was the translation and cultural adaptation of the CLEFT-Q t... more Background The purpose of this study was the translation and cultural adaptation of the CLEFT-Q to Farsi and evaluating the reliability of it. Methods The English version of the CLEFT-Q was translated to Farsi following the guidelines set forth by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). To calculate the reliability, 50 participants filled out the Farsi version of the questionnaire twice at 2-week intervals. Results The difficulties during the translation and cultural adaptation process were as follows: 7.56% of items from the independent forward translations, 62.18% of items from the comparison between two forward translations, and 21% of items from the comparison between post-back translation and the original version. The internal consistency and stability of the Farsi version of the CLEFT-Q were 0.979 and 0.997, which both were categorized as excellent. Conclusion The Farsi version of the CLEFT-Q is a valid and reliable tool currently availab...
Journal of Biomedical Physics and Engineering, 2016
Background: There are many studies to investigate the effects of each interacting component of tu... more Background: There are many studies to investigate the effects of each interacting component of tumor-immune system interactions. In all these studies, the distinct effect of each component was investigated. As the interaction of tumor-immune system has feedback and is complex, the alternation of each component may affect other components indirectly.Objective: Because of the complexities of tumor-immune system interactions, it is important to determine the mutual behavior of such components. We need a careful observation to extract these mutual interactions. Achieving these observations using experiments is costly and time-consuming.Methods: To achieve these observations, we presented a fuzzy structured agent-based model of tumor-immune system interactions. In this study, we consider the confronting of the effector cells of the adaptive immune system in the presence of the cytokines of interleukin-2 (IL-2) and transforming growth factor-beta (TGF-β) as a fuzzy structured model. Using...
The anti proliferative and cytotoxic activity of sodium butyrate (SB) as a microbial product on h... more The anti proliferative and cytotoxic activity of sodium butyrate (SB) as a microbial product on human colorectal carcinoma cell lines Background: Sodium butyrate (SB), a short chain fatty acid, is a histone deacetylase inhibitor (HDI) and produced in the colonic lumen as a consequence of anaerobic bacterial fermentation of dietary fiber, undigested starch and proteins. SB serves as an energy source of colonic epithelium and plays a role in the maintenance of colonic homeostasis; in addition HDIs induce growth arrest and apoptosis in a variety of human cancer cells. Colorectal cancer metastases result in a significant number of cancer related deaths. Methods: The viability of cells was measured by MTT assay. The adherent SW480 and HCT116 human colorectal carcinoma cells were seeded in 96-well plates. Different concentrations of SB (0, 1.0, 2.5, 5.0, 10, 20 μmol/L) were added and then incubated for 12, 24, 48, and 72 hours at 37°C with 5% CO2. MTT solution was added to each well. Dime...
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2017
Dendritic cells are important in initiating immune responses; therefore, a range of dendritic cel... more Dendritic cells are important in initiating immune responses; therefore, a range of dendritic cell-based approaches have been established to induce immune response against cancer cells. However, the presence of immunosuppressive mediators such as adenosine in the tumor microenvironment reduces the efficacy of dendritic cell-based cancer immunotherapy. In this study, we investigated whether blockade of the A2A adenosine receptor with a selective antagonist and a CD73 inhibitor may increase the efficacy of a dendritic cell-based cancer vaccine. According to the findings, this therapeutic combination reduced tumor growth, prolonged survival of tumor-bearing mice, and enhanced specific antitumor immune responses. Thus, we suggest that targeting cancer-derived adenosine improves the outcomes of dendritic cell-based cancer immunotherapy.
CD137 (ILA/4‐1BB), a member of tumor necrosis factor receptor superfamily, is one of the most imp... more CD137 (ILA/4‐1BB), a member of tumor necrosis factor receptor superfamily, is one of the most important T cell costimulatory molecules. Interaction of this molecule with its ligand transmits a two‐way signal that activates both T lymphocyte and antigen presenting cells. The soluble form of CD137 (sCD137) reduces the activity of its membrane isoform and is associated with T lymphocyte activation‐induced cell death. Recombinant CD137‐Fc may be used to treat cancers, autoimmune disorders and viral infections. It may also be useful for management of coronavirus infection. The 1276 bp DNA sequence encoded CD137‐Fc recombinant protein was prepared and subcloned into lentiviral vector and expressed in transduced CHO‐K1 eukaryotic cells. The sodium dodecyl sulfate–polyacrylamide gel electrophoresis, Western blot analysis, and enzyme‐linked immunosorbent assay analysis results demonstrated that the expression of the 70‐kDa CD137‐Fc molecule was detectable without any degradation. This study helps to confirm previous research suggesting the use of this recombinant protein as a promising solution for the treatment of virus infections. CD137‐Fc fusion protein could also make immunotherapy more effective for some diseases. This product is widely used in novel medical treatments, including cell‐based immunotherapy such as dendritic cell, CAR T and CAR NK therapy. Its production and usage in research and treatment is noticeable also in current coronavirus disease 2019 pandemic.
The efficacy of conventional anti-tumor immunotherapeutic approaches is markedly affected by the ... more The efficacy of conventional anti-tumor immunotherapeutic approaches is markedly affected by the immunosuppressive microenvironment of tumor. Since adenosine is one of the main orchestra leaders in immunosuppression symphony of tumor, targeting its producing molecules such as CD73 can help to achieve a better clinical outcome following conventional cancer immunotherapeutic approaches. In the present study, we evaluated the efficacy of CD73-specific siRNA-loaded chitosan-lactate nanoparticles (ChLa NPs) in combination with tumor lysate pulsed dendritic cells (DCs) vaccine in treatment of 4T1 (murine derived) breast cancer bearing mice. Our results showed that intravenous administration of CD73-specific siRNA-loaded NPs led to reduced expression of CD73 in tumor cells which was associated with decreased tumor growth and metastasis, and improved mice survival. Furthermore, we found that the mechanism by which combination therapy inhibits tumor growth is in part related to downregulatio...
ABSTRACT We assessed the effect of sodium butyrate (SB) as a histone deacetylase inhibitor (HDACi... more ABSTRACT We assessed the effect of sodium butyrate (SB) as a histone deacetylase inhibitor (HDACi) on Toll-like receptor 4 (TLR4) gene expression levels, in low TLR4 expressing (HCT116) and high TLR4 expressing (SW480) colorectal cancer cells. The cytotoxic effect of SB was assessed by culturing SW480 and HCT116 cell lines using a broad spectrum of times and concentrations of SB. The MTT assay was done to check the cytotoxic properties of different SB concentrations. Gene expression levels of TLR4 was then evaluated for non-cytotoxic SB concentrations. Morphological analysis and MTT assay confirmed that SB concentrations equal to or less than 5mM were not cytotoxic for both cell lines. At 5mM concentration of SB in SW480 cell line and 1mM concentration of SB in HCT116 cell line, TLR4 gene expression level significantly increased from 24 to 48 hrs and decreased significantly from 48 to 72 hrs with an “early increased and late decreased pattern”. At 1mM concentration of SB in SW480 cell line and 5mM concentration of SB in HCT116 cell line, TLR4 expression had a “gradually increased pattern”. This study focuses on the dose-time-effect of SB in the pathogenesis of colorectal cancer. SB alters the expression level of TLR4 in colorectal cancer cells. This effect may depend on the cell type, treatment duration and SB concentration. The alterations in TLR4 expression may be due to the direct effect of SB on TLR4 and/or the expression changes of in other genes which may indirectly affect the TLR4 expression. Abbreviations: TLR4: Toll-like receptor 4; HDACi: histone deacetylase inhibitor; SB: sodium Butyrate; CRC: colorectal cancer; SCFA: short-chain fatty acid; hrs: hours
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2017
Dendritic cells are important in initiating immune responses; therefore, a range of dendritic cel... more Dendritic cells are important in initiating immune responses; therefore, a range of dendritic cell-based approaches have been established to induce immune response against cancer cells. However, the presence of immunosuppressive mediators such as adenosine in the tumor microenvironment reduces the efficacy of dendritic cell-based cancer immunotherapy. In this study, we investigated whether blockade of the A2A adenosine receptor with a selective antagonist and a CD73 inhibitor may increase the efficacy of a dendritic cell-based cancer vaccine. According to the findings, this therapeutic combination reduced tumor growth, prolonged survival of tumor-bearing mice, and enhanced specific antitumor immune responses. Thus, we suggest that targeting cancer-derived adenosine improves the outcomes of dendritic cell-based cancer immunotherapy.
This study is designed to present an agent-based model (ABM) to simulate the interactions between... more This study is designed to present an agent-based model (ABM) to simulate the interactions between tumor cells and the immune system in the melanoma model. The Myeloid-derived Suppressor Cells (MDSCs) and dendritic cells (DCs) are considered in this model as immunosuppressive and antigen-presenting agents respectively.The animal experiment was performed on 68 B16F10 melanoma tumor-bearing C57BL/6 female mice to collect dynamic data for ABM implementation and validation. Animals were divided into 4 groups; group 1 was control (no treatment) while groups 2 and 3 were treated with DC vaccine and low-dose 5- fluorouracil (5-FU) respectively and group 4 was treated with both DC Vaccine and low-dose of 5-FU. The tumor growth rate, number of MDSC, and presence of CD8+/CD107a+ T cells in the tumor microenvironment were evaluated in each group. Firstly, the tumor cells, the effector immune cells, DCs, and the MDSCs have been considered as the agents of the ABM model and their interaction meth...
Additional file 1. Table S1. Examples of Discrepancies between the Original English Version and B... more Additional file 1. Table S1. Examples of Discrepancies between the Original English Version and Back-translated English Version.
Background: The 4T1 cells tumor growth and metastatic pattern in BALB/c mice very closely mimic h... more Background: The 4T1 cells tumor growth and metastatic pattern in BALB/c mice very closely mimic human breast cancer. These herbal remedies used in traditional folk medicine have been the source of many medically beneficial drugs. The aim of the current study was to evaluate the anti-proliferative activity of the asafoetida, ginseng and fennel ethanolic extracts on mouse breast cancer 4T1 cell-line invitro.Method: in this experimental study, Asafoetida, gensing and fennel were extracted; 4T1 mouse mammary tumor cell line were cultured in 48-well flat bottom plate in density of 50x103 per well in 100 µl RPMI1640 medium then different dilutions of each extract (25 , 50, 100, 200, 500, and 2000 μg/ml) were added to cell culture. Cells then were incubated at 37 oC for 24 hours. After 24 h, cell Proliferation was determined by the BRDU assay . dataset of experiments were collected and analysed with SPSS19 software. Significant level of Data was Examined with one-way ANOVA method and P
The goal of this study is introducing a quantified feature for investigating the quality manner a... more The goal of this study is introducing a quantified feature for investigating the quality manner and interaction between the immune system and tumor cell. For this purpose, we introduced an agent based model which uses two agents, consists tumor cell and CD8+ cells and the environment which consists IL-2 and TGF- β cytokines. This model works using a variety of ratios. The most important ratio of this model is the tumor’s proliferation ratio. We investigated this ratio in three states of tumor-immune system interaction consist elimination, equilibrium and escape using a raw model, then this ratio investigated using models which optimized by experimental data. The results showed that, if model be leaning to the elimination state, this ratio falls faster and if be leaning to the escape state, this ratio will reduce slowly. This result proved by models which used experimental data for optimizing. Therefore, using this ratio we can compare the different manner of tumor-immune system inte...
BACKGROUND Melanoma progression and metastasis is suggested to be mediated by increased accumulat... more BACKGROUND Melanoma progression and metastasis is suggested to be mediated by increased accumulation of myeloid derived suppressor cells. Various chemotherapeutic drugs such as 5-Fluorouracil in single low concentration have the capacity, at least in part, to reverse tumor progression by reducing myeloid derived suppressor cells-mediated immunosuppression. OBJECTIVE To assess whether multiple low doses of 5-fluorouracil could repress myeloid derived suppressor cells in low frequency and, in turn, could enhance anti-tumor responses and promote a more prolonged survival in a murine melanoma model. METHODS Fifty milligram per kilogram body weight dose of 5-Flourouracil was administered intraperitoneally 4 times with 3-day intervals to C57BL/6 mice after B16 melanoma tumor models were established. The frequency and suppressive functions of myeloid derived suppressor cells and induction of anti-tumor CD8+ T cells as well as tumor growth and survival were evaluated in drug treated and unt...
Otosclerosis is a common cause of conductive hearing loss. It is surgically treated with stapedec... more Otosclerosis is a common cause of conductive hearing loss. It is surgically treated with stapedectomy or stapedotomy. Sensory- neural hearing loss is an uncommon but known complication of this surgery. A 25-year-old Iranian female patient with bilateral otosclerosis underwent right stapedotomy and developed bilateral sensorineural hearing loss a few days after the surgery which recovered with appropriate treatment. The possible causes and their clinical courses are discussed in this study. Sensorineural hearing loss after stapedotomy has many different etiologies. Generally, causes which are not directly related to the surgery should also be considered.
Background The purpose of this study was the translation and cultural adaptation of the CLEFT-Q t... more Background The purpose of this study was the translation and cultural adaptation of the CLEFT-Q to Farsi and evaluating the reliability of it. Methods The English version of the CLEFT-Q was translated to Farsi following the guidelines set forth by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). To calculate the reliability, 50 participants filled out the Farsi version of the questionnaire twice at 2-week intervals. Results The difficulties during the translation and cultural adaptation process were as follows: 7.56% of items from the independent forward translations, 62.18% of items from the comparison between two forward translations, and 21% of items from the comparison between post-back translation and the original version. The internal consistency and stability of the Farsi version of the CLEFT-Q were 0.979 and 0.997, which both were categorized as excellent. Conclusion The Farsi version of the CLEFT-Q is a valid and reliable tool currently availab...
Journal of Biomedical Physics and Engineering, 2016
Background: There are many studies to investigate the effects of each interacting component of tu... more Background: There are many studies to investigate the effects of each interacting component of tumor-immune system interactions. In all these studies, the distinct effect of each component was investigated. As the interaction of tumor-immune system has feedback and is complex, the alternation of each component may affect other components indirectly.Objective: Because of the complexities of tumor-immune system interactions, it is important to determine the mutual behavior of such components. We need a careful observation to extract these mutual interactions. Achieving these observations using experiments is costly and time-consuming.Methods: To achieve these observations, we presented a fuzzy structured agent-based model of tumor-immune system interactions. In this study, we consider the confronting of the effector cells of the adaptive immune system in the presence of the cytokines of interleukin-2 (IL-2) and transforming growth factor-beta (TGF-β) as a fuzzy structured model. Using...
The anti proliferative and cytotoxic activity of sodium butyrate (SB) as a microbial product on h... more The anti proliferative and cytotoxic activity of sodium butyrate (SB) as a microbial product on human colorectal carcinoma cell lines Background: Sodium butyrate (SB), a short chain fatty acid, is a histone deacetylase inhibitor (HDI) and produced in the colonic lumen as a consequence of anaerobic bacterial fermentation of dietary fiber, undigested starch and proteins. SB serves as an energy source of colonic epithelium and plays a role in the maintenance of colonic homeostasis; in addition HDIs induce growth arrest and apoptosis in a variety of human cancer cells. Colorectal cancer metastases result in a significant number of cancer related deaths. Methods: The viability of cells was measured by MTT assay. The adherent SW480 and HCT116 human colorectal carcinoma cells were seeded in 96-well plates. Different concentrations of SB (0, 1.0, 2.5, 5.0, 10, 20 μmol/L) were added and then incubated for 12, 24, 48, and 72 hours at 37°C with 5% CO2. MTT solution was added to each well. Dime...
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2017
Dendritic cells are important in initiating immune responses; therefore, a range of dendritic cel... more Dendritic cells are important in initiating immune responses; therefore, a range of dendritic cell-based approaches have been established to induce immune response against cancer cells. However, the presence of immunosuppressive mediators such as adenosine in the tumor microenvironment reduces the efficacy of dendritic cell-based cancer immunotherapy. In this study, we investigated whether blockade of the A2A adenosine receptor with a selective antagonist and a CD73 inhibitor may increase the efficacy of a dendritic cell-based cancer vaccine. According to the findings, this therapeutic combination reduced tumor growth, prolonged survival of tumor-bearing mice, and enhanced specific antitumor immune responses. Thus, we suggest that targeting cancer-derived adenosine improves the outcomes of dendritic cell-based cancer immunotherapy.
CD137 (ILA/4‐1BB), a member of tumor necrosis factor receptor superfamily, is one of the most imp... more CD137 (ILA/4‐1BB), a member of tumor necrosis factor receptor superfamily, is one of the most important T cell costimulatory molecules. Interaction of this molecule with its ligand transmits a two‐way signal that activates both T lymphocyte and antigen presenting cells. The soluble form of CD137 (sCD137) reduces the activity of its membrane isoform and is associated with T lymphocyte activation‐induced cell death. Recombinant CD137‐Fc may be used to treat cancers, autoimmune disorders and viral infections. It may also be useful for management of coronavirus infection. The 1276 bp DNA sequence encoded CD137‐Fc recombinant protein was prepared and subcloned into lentiviral vector and expressed in transduced CHO‐K1 eukaryotic cells. The sodium dodecyl sulfate–polyacrylamide gel electrophoresis, Western blot analysis, and enzyme‐linked immunosorbent assay analysis results demonstrated that the expression of the 70‐kDa CD137‐Fc molecule was detectable without any degradation. This study helps to confirm previous research suggesting the use of this recombinant protein as a promising solution for the treatment of virus infections. CD137‐Fc fusion protein could also make immunotherapy more effective for some diseases. This product is widely used in novel medical treatments, including cell‐based immunotherapy such as dendritic cell, CAR T and CAR NK therapy. Its production and usage in research and treatment is noticeable also in current coronavirus disease 2019 pandemic.
The efficacy of conventional anti-tumor immunotherapeutic approaches is markedly affected by the ... more The efficacy of conventional anti-tumor immunotherapeutic approaches is markedly affected by the immunosuppressive microenvironment of tumor. Since adenosine is one of the main orchestra leaders in immunosuppression symphony of tumor, targeting its producing molecules such as CD73 can help to achieve a better clinical outcome following conventional cancer immunotherapeutic approaches. In the present study, we evaluated the efficacy of CD73-specific siRNA-loaded chitosan-lactate nanoparticles (ChLa NPs) in combination with tumor lysate pulsed dendritic cells (DCs) vaccine in treatment of 4T1 (murine derived) breast cancer bearing mice. Our results showed that intravenous administration of CD73-specific siRNA-loaded NPs led to reduced expression of CD73 in tumor cells which was associated with decreased tumor growth and metastasis, and improved mice survival. Furthermore, we found that the mechanism by which combination therapy inhibits tumor growth is in part related to downregulatio...
ABSTRACT We assessed the effect of sodium butyrate (SB) as a histone deacetylase inhibitor (HDACi... more ABSTRACT We assessed the effect of sodium butyrate (SB) as a histone deacetylase inhibitor (HDACi) on Toll-like receptor 4 (TLR4) gene expression levels, in low TLR4 expressing (HCT116) and high TLR4 expressing (SW480) colorectal cancer cells. The cytotoxic effect of SB was assessed by culturing SW480 and HCT116 cell lines using a broad spectrum of times and concentrations of SB. The MTT assay was done to check the cytotoxic properties of different SB concentrations. Gene expression levels of TLR4 was then evaluated for non-cytotoxic SB concentrations. Morphological analysis and MTT assay confirmed that SB concentrations equal to or less than 5mM were not cytotoxic for both cell lines. At 5mM concentration of SB in SW480 cell line and 1mM concentration of SB in HCT116 cell line, TLR4 gene expression level significantly increased from 24 to 48 hrs and decreased significantly from 48 to 72 hrs with an “early increased and late decreased pattern”. At 1mM concentration of SB in SW480 cell line and 5mM concentration of SB in HCT116 cell line, TLR4 expression had a “gradually increased pattern”. This study focuses on the dose-time-effect of SB in the pathogenesis of colorectal cancer. SB alters the expression level of TLR4 in colorectal cancer cells. This effect may depend on the cell type, treatment duration and SB concentration. The alterations in TLR4 expression may be due to the direct effect of SB on TLR4 and/or the expression changes of in other genes which may indirectly affect the TLR4 expression. Abbreviations: TLR4: Toll-like receptor 4; HDACi: histone deacetylase inhibitor; SB: sodium Butyrate; CRC: colorectal cancer; SCFA: short-chain fatty acid; hrs: hours
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2017
Dendritic cells are important in initiating immune responses; therefore, a range of dendritic cel... more Dendritic cells are important in initiating immune responses; therefore, a range of dendritic cell-based approaches have been established to induce immune response against cancer cells. However, the presence of immunosuppressive mediators such as adenosine in the tumor microenvironment reduces the efficacy of dendritic cell-based cancer immunotherapy. In this study, we investigated whether blockade of the A2A adenosine receptor with a selective antagonist and a CD73 inhibitor may increase the efficacy of a dendritic cell-based cancer vaccine. According to the findings, this therapeutic combination reduced tumor growth, prolonged survival of tumor-bearing mice, and enhanced specific antitumor immune responses. Thus, we suggest that targeting cancer-derived adenosine improves the outcomes of dendritic cell-based cancer immunotherapy.
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