Dendritic cells in cancer immunotherapy from bench to clinic
Mohamed
Salem
Professor of Immunology
Immunology & Biotechnology Division
Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt
author
text
article
2019
eng
Generation of robust immunity against microbial infection and cancers require fine-tuned interaction between the components of innate and adaptive arms of immune system. Dendritic cells (DCs) are the central player of innate immune arm that bridge innate to adaptive immunity. These cells are effective at antigen uptake, killing, processing and presentation of the processed small and large peptides (MHC class-I and class-II proteins) to cytotoxic CD8+ and helper CD4+ T cells, respectively. Upon recognition of the presented peptides by T cells (signal 1) concomitant interaction of the costimulatory molecules CD80 and CD40 on DCs with their ligands CD28 and CD40L (signal 2) on T cells, DCs and T cells become activated. However, full activation and proliferation of DCs and T cells also require induction of inflammatory cytokines (signal 3) such as IL-1, IL-6, IL-12, IFN- α and TNF-α. Signal 3 is ultimately induced by the interaction of toll like receptors (TLRs) highly expressed on innate immune cells in particular DCs, with different natural or synthetic microbial products (TLR ligands). Due to the morphological features of DCs and extension of thousands of dendrites from their surface, these cells are several fold higher at uptaking, processing, and presenting foreign antigens than macrophages. They are also more capable of interaction with TLR ligands than other innate immune cells. As such, DCs are of paramount significance to generation of effector 1ry immunity upon encountering the 1st antigen exposure and then generation of resting memory cells capable of mounting robust 2nd immunity. DCs, however, are dysfunctional in the presence of cancer due to secretion of several toxic factors by cancer cells. Therefore, ex vivo generation of DCs either from hematopoietic cells or from monocytes is one potential alternative to restore the functions of these cells and their role in bridging innate and adaptive immunity. Upon their generation in vitro they are activated by TLR ligands and pulsed with the desired tumor antigens. Then, DCs are injected back to the same patient with the goal to activate endogenous tumor specific T cells. DCs can be pulsed with different forms of antigens, including peptides, proteins, tumor cell lysate, RNA or naked DNA. Both preclinical and clinical studies have demonstrated promising anti-tumor responses after treatment with DC-based vaccination against both hematological and solid tumors. To optimize its clinical applications, recent studies have been focusing on how to: 1) speed up the generation of these cells in vitro, 2) maximize their activation in vitro, 3) using allogenic DCs rather than personalized DCs, 4) their combination with other immunotherapy modalities and 5) how to induce their activation in vivo upon their adoptive transfer. In our own experience, we have been able to generate DCs from mouse and human and to induce their activation in vitro and in vivo with TLR3 ligand. We have also used them to vaccinate against pancreatic cancer and the results showed promising clinical responses with minimal toxicity. We do believe that DC-based vaccination can optimize the effective immunotherapy based on the use checkpoint inhibitors as well as CAR cells. Future studies are needed to address this hypothesis.
International Journal of Cancer and Biomedical Research
The Egyptian Association for Cancer Research (EACR)
2682-261X
3
v.
3
no.
2019
1
1
https://jcbr.journals.ekb.eg/article_63103_d8a6e1102f52d6213f503814a1119d96.pdf
High expression of the checkpoint molecule PD-1 on conventional CD4+ and regulatory T cells in the peripheral blood of Hepatocellular carcinoma patients
Mohamed
Salem
Professor of Immunology
Immunology & Biotechnology Division
Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt
author
Nadia
Elwan
Tropical Medicine and Infectious Disease Department, Faculty of Medicine, Tanta University, Egypt.
author
Ibrahim
ElShourbgy
Department of Zoology, Faculty of Science, Tanta University, Tanta.
author
Hanan
Elokeil
Center of Excellence of Cancer Research, Tanta University Educational Hospital
author
text
article
2019
eng
Background: Regulatory T cells (Tregs), possess a suppression function leading to T cells exhaustion and tumor progression through serious of signaling pathways of inhibitory receptors under pathological conditions in particular cancer including hepatocellular carcinoma. Conventional helper CD4+ T cells can be converted into regulatory T cells that may suppress anti HCC immunity through different mechanisms including expression of PD-1. PD-1 inhibitory checkpoint and its ligand PDL-1 emerge immune escape through interaction between T cell and tumor microenvironment. Aim: The aim of this study is to analyze the expression level of the regulatory checkpoint (PD-1) on T cells in HCC patients. Materials and methods: The numbers of conventional and regulatory T cells and their expression of checkpoint receptor PD-1 were analyzed in the peripheral blood of HCC patients (n=20) as well as healthy control volunteers (n=15) using multi-parametric flow cytometry after staining with anti-CD4, anti-CD25, anti-CD127 for (T cells) and anti PD-1 (CD279). Results: As compared to healthy control volunteers HCC patients showed high relative numbers of Tregs expressing CD4+CD25+CD127- and decrease relative number of conventional CD4+ defines as CD4+CD25-CD127-. These cells showed high expression by increasing level of PD-1 where CD4+ showed high expression than Tregs. Similar cells number of PD-1 expression where observed at the level of absolute numbers. Conclusion: HCC patients before treatment express high level of the checkpoint molecule PD-1 opening the door for further investigations.
International Journal of Cancer and Biomedical Research
The Egyptian Association for Cancer Research (EACR)
2682-261X
3
v.
3
no.
2019
2
7
https://jcbr.journals.ekb.eg/article_63386_d41d8cd98f00b204e9800998ecf8427e.pdf
Comparing the possible anti-tumor effects of synthetic chalcones and metal complexes in a tumor mouse model
Asmaa
El Gamal
Department of Zoology, Faculty of Science, Tanta University, Egypt
author
Mohamed
Nasef
Immunology and Biotechnology Unit, Zoology Department, Faculty of Science, Tanta University, 31527 Tanta, Egypt
author
Mohamed
Gaber
Department of Chemistry, Faculty of Science, Tanta University, Egypt
author
Mohamed
Salem
Immunology and Biotechnology Unit,
Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt
author
text
article
2019
eng
Introduction: Traditional treatment of cancer by using chemotherapy not only kills cancer cells but also, normal cells and failed in preventing the spread of the tumor. Chalcone have several biological activities, such as antioxidant, antibacterial, antifungal, anti-inflammatory, and anti-tumor. Aim: To compare the antitumor effects of chalcones in Ehrlich ascetic carcinoma (EAC) bearing mice. Materials and Method: Female Swiss albino mice were randomly divided into 6 groups as the following; Group 1 were served as a negative control, group 2 were inoculated with 2.5×105 (EAC) cells, group 3 were inoculated with 2.5×105 EAC cells and then treated with cisplatin (2 mg/kg), group 4 were inoculated with 2.5×105 EAC cells and then treated with chalcone 1 (0.3 ml gm/L), group 5 were inoculated with 2.5×105 EAC cells and then treated with chalcone II (0.3 ml gm/L). After 7 days, all groups of mice were sacrificed to measure the number and cell cycle of tumor cells as well as the number and activation of CD8+ T cells. Results: Treatment of tumor-bearing mice with chalcone I, but not chalcone II induced decreases in the total number of live cells when compared to control tumor-bearing mice, coinciding with significant increases in G0, G1, S and G2 phases of EAC cells which were comparable to the effects of cisplatin. As compared to control tumor-bearing mice, tumor cells harvested from mice treated with chalcone I showed significant increases in the numbers of activated CD8+ T cells. Conclusion: Chalcone I possesses anti-tumor effects by inducing tumor cells arrest and activation of T cells.
International Journal of Cancer and Biomedical Research
The Egyptian Association for Cancer Research (EACR)
2682-261X
3
v.
3
no.
2019
17
27
https://jcbr.journals.ekb.eg/article_65449_d41d8cd98f00b204e9800998ecf8427e.pdf
dx.doi.org/10.21608/jcbr.2019.65449
Effect of Balanitoside and Gemcitabine on serum biochemistry during mouse lung carcinogenesis
Elsayed
Salim
Zoology Department, Research Lab. of Molecular Carcinogenesis
author
Fouad
Abou-Zaid
Zoology Department, Research Lab. of Molecular Carcinogenesis
author
Abeer
Khamis
Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta 31527, Egypt
author
Sara
Abou-Eisha
Zoology Department, Research Lab. of Molecular Carcinogenesis
author
text
article
2019
eng
Background: Gemcitabine is utilized as a standard anti malignancy chemotherapy. Its use, however, is limited due to the associated serious side effects. Aim: The aim of the present study is to study the impact of balanitoside, extracted from Balanites aegyptiaca fruits on mouse serum biochemistry during chemically-induced lung cancer. Methods: Mice were treated with the carcinogen (Ure+ BHT) to induce lung carcinogenesis and then left without treatment, treated gemcitabine, or both gemcitabine and balanitoside. Results: Our results reveal that elevated serum levels of alanine and aspartate transaminases caused by Ure+BHT injection were inhibited in mice treated with the ethanolic extract of B. aegyptiaca, indicating to its hepatoprotective actions either alone combined with gemcitabine. Also, the doses of B. aegyptiaca extract used here enhanced the renal function parameters as it improved the changes induced by Ure+BHT occurred in serum creatinine and uric acid levels. Moreover, the present data showed increased serum cholesterol, triglyceride, and low-density lipoprotein (LDL) levels and a decrease in high-density lipoprotein (HDL) levels after carcinogen-treatment when compared with the control normal group. These changes were ameliorated after treatment with B. aegyptiaca either alone or combined with gemcitabine. Conclusion: B. aegyptiaca extract has significant modulatory effects and chemo-preventive properties against biochemical changes during lung carcinogenesis, indicating to its prophylactic anti-toxic effect.
International Journal of Cancer and Biomedical Research
The Egyptian Association for Cancer Research (EACR)
2682-261X
3
v.
3
no.
2019
28
33
https://jcbr.journals.ekb.eg/article_65450_d41d8cd98f00b204e9800998ecf8427e.pdf
Effect of Moringa oleifera on antioxidant enzymes and oxidative stress induced by aluminium exposure in male albino rat testes
Hala
Abdelazem
Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt
author
text
article
2019
eng
This study summarizes the effect of Moringa oleifera leaves extract on oxidative stress-induced from exposure to aluminium (aluminium chloride, AlCl₃) on testes of male albino rats. Fifteen male albino rats (250.0±10.0) g were divided into five groups, each group of 10 rats. Group one received sterile water orally as a control, group two received AlCl₃ (50mg/kg/day), group three received M. oleifera (300mg/kg/day), group four received AlCl3 (50mg/kg/day) for four weeks then M. oleifera (300mg/kg/day) for four weeks and last group five received AlCl₃ and M. oleifera for eight weeks. The results showed significant changes in testes parameters where there was a decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione -s-transferase (GST) and glutathione peroxidase (GPx) associated with increase in the activity of xanthine oxidase (XO) and malondialdehyde (MDA) levels in aluminium treated groups. Also, there was an improvement in the activity of the enzymes (SOD, CAT, GST, and GPx) associated with a decrease in the activity of XO and MDA in groups received M. oleifera. These results proved that M. oleifera has an ameliorative effect on the activities of antioxidant enzymes and oxidative stress-induced from exposure to aluminium in male albino rats.
International Journal of Cancer and Biomedical Research
The Egyptian Association for Cancer Research (EACR)
2682-261X
3
v.
3
no.
2019
34
41
https://jcbr.journals.ekb.eg/article_66836_b469db1d7389e5f769b0c11fc07f98e7.pdf