eng
Shiraz Institute for Cancer Research
Iranian Journal of Immunology
1735-1383
1735-367X
2016-09-01
13
3
148
166
33404
Whole Tumor Cell Vaccine Adjuvants: Comparing IL-12 to IL-2 and IL-15
Abdolkarim Sheikhi
sheikhi@queensu.ca
1
Abdollah Jafarzadeh
jafarzadeh14@yahoo.com
2
Parviz Kokhaei
p_kokha@yahoo.com
3
Mohammad Hojjat-Farsangi
4
Department of Immunology, Dezful University of Medical Sciences, Dezful, Iran
Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman
Cancer Research Center, Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
Immune and Gene Therapy Laboratory, Department of Oncology-Pathology, Karolinska Cancer Center, Karolinska University Hospital, Solna and Karolinska Institute, Stockholm, Sweden
Cancer immunotherapy (passive or active) involves treatments which promote the ability of the immune system to fight tumor cells. Several types of immunotherapeutic agents, such as monoclonal antibodies, immune checkpoint inhibitors, non-specific immunomodulatory agents, and cancer vaccines are currently under intensive investigation in preclinical and clinical trials. Cancer vaccines induce permanent activation of the immune system and may be considered the most promising method for cancer treatment, especially in combination with other agents of passive immunotherapy. Among various approaches to cancer vaccines, whole tumor cell vaccines have been attracting attention for several years. Despite their low to moderate clinical effects, these vaccines have numerous advantages. Their ability to generate immune responses against tumor-associated antigens reduces the possibility for tumor cells to escape and facilitates the development of “off-the-shelf” allogeneic tumor vaccines. Understanding the reciprocal interactions between tumor cells and leukocytes is a key to harness the full potential of whole cell vaccination. Cytokines are considered as potent immunomodulatory molecules which behave as adjuvants in whole tumor cell vaccines. Improved mechanistic understanding of key cytokines in tumor immunity will serve as a resource for rational design of whole cell cancer vaccines. Although there are several reports about the use of different immunostimulatory cytokines as adjuvants, interleukin (IL)-12 appears to have superior effects compared to other cytokines. This review describes the effects of IL-12 compared to other immunomodulatory cytokines, such as IL-2 and IL-15, and highlights its application in whole cell tumor vaccination.
https://iji.sums.ac.ir/article_33404_23d30245ee6d15da7720424bf5957ee2.pdf
cancer
Cytokines
immunotherapy
Tumor Vaccines
eng
Shiraz Institute for Cancer Research
Iranian Journal of Immunology
1735-1383
1735-367X
2016-09-01
13
3
167
177
33405
مقاله پژوهشی
Regulatory T Cells and Myeloid-Derived Suppressor Cells in Patients with Peptic Ulcer and Gastric Cancer
Hamideh Mesali
1
Abolghasem Ajami
ajami_ghasem@hotmail.com
2
Hadi Hussein-Nattaj
3
Alireza Rafiei
rafiei1710@gmail.com
4
Zeinab Rajabian
5
Hossein Asgarian-Omran
6
Vahid Hosseini
7
Tarang Taghvaei
8
Mohsen Tehrani
drmtehrani@gmail.com
9
Department of Immunology, School of Medicine
Department of Immunology, School of Medicine
Department of Immunology, School of Medicine
Department of Immunology, School of Medicine
Department of Immunology, School of Medicine
Department of Immunology, School of Medicine
Inflammatory Diseases of Upper Gastrointestinal Tract Research Center, Imam Hospital, Mazandaran University of Medical Sciences, Sari, Iran
Inflammatory Diseases of Upper Gastrointestinal Tract Research Center, Imam Hospital, Mazandaran University of Medical Sciences, Sari, Iran
Department of Immunology, School of Medicine
Background: Regulatory T Cells (Tregs) and Myeloid-Derived Suppressor Cells (MDSCs) are two main regulatory cells modulating the immune responses in inflammation and cancer. Objective: To investigate and compare Tregs and MDSCs in peptic ulcer and gastric cancer. Methods: Patients with dyspepsia were selected and divided into three groups of non-ulcer dyspepsia (NUD, n=22), peptic ulcer disease (PUD, n=25), and gastric cancer (GC, n=27) according to their endoscopic and histopathological examinations. Helicobacter pylori infection was diagnosed by rapid urease test and histopathology. The number of peripheral blood CD4+CD25+FoxP3+Tregs and CD14+HLA-DR- MDSCs were determined in all patients, by flow cytometry. The number of FoxP3+ regulatory T cells was also determined by immunohistochemistry (IHC). Results: The percentage of peripheral blood Treg cells in both PUD )0.81 ± 0.39, p<0.001) and GC groups )0.98 ± 0.65, p<0.001) were significantly higher than in NUD group (0.46 ± 0.10). These results were also confirmed by IHC. A significantly higher percentage of MDSCs in patients with PUD )0.73 ± 0.19, p<0.001) and GC )0.73 ± 0.16, p<0.001) was also observed when compared to NUD group )0.46 ± 0.16). There was no difference in the percentages of these two cell types between the PUD and GC groups. The percentages of Tregs and MDSCs in patients with PUD and GC were not significantly correlated. Conclusions: Both Tregs and MDSCs showed higher frequencies in PUD and GC. These results suggest that immune-modulation by the Tregs and MDSCs may play a role in the pathogenesis of PUD and GC.
https://iji.sums.ac.ir/article_33405_dcc4749123820d04513037ff8807fe0c.pdf
Gastric Cancer
Myeloid-Derived Suppressor Cell
peptic ulcer
Regulatory T cells
eng
Shiraz Institute for Cancer Research
Iranian Journal of Immunology
1735-1383
1735-367X
2016-09-01
13
3
178
185
33406
مقاله پژوهشی
Natural Killer Cell Cytotoxicity Against SKOV3 after HLA-G Downregulation by shRNA
Nazanin Nazari
1
Shirin Farjadian
farjadsh@sums.ac.ir
2
Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran
Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran
Background: HLA-G is a nonclassical HLA class I molecule which, when elevated in tumor cells, is one of the main factors involved in tumor evasion of immune responses including NK and T cells. Objective: To evaluate the effect of HLA-G downregulation on NK cell cytotoxicity in tumor cell lines. Methods: The expression level of HLA-G was measured by real-time PCR and flowcytometry after transfection of SKOV3 by shRNA.1, which targets specific sequences in exon 4, or shRNA.2, which targets both exons 4 and 6. NK-92MI cell cytotoxicity against transfected or untransfected target cell lines was measured with the lactate dehydrogenase (LDH) release assay. The Jeg-3 cell line was used as a positive control. Results: Membrane-bound HLA-G expression levels decreased significantly in both cell lines after transfection with both shRNAs compared to their corresponding untransfected cells (p<0.05). Jeg-3 cells were better lysed than SKOV3 cells by NK cells during the first 48 h after transfection with both shRNAs. Compared to untransfected cells, shRNA.1-transfected SKOV3 cells were significantly more lysed by NK cells 24 h post-transfection (p=0.043). Conclusion: As a clinical approach, HLA-G downregulation with shRNA may be effective in cancer therapy by improving immune cell activation.
https://iji.sums.ac.ir/article_33406_99c837976dcbd07ce18ad6f3657c006a.pdf
HLA-G downregulation
shRNA
SKOV3
NK cell cytotoxicity
eng
Shiraz Institute for Cancer Research
Iranian Journal of Immunology
1735-1383
1735-367X
2016-09-01
13
3
186
196
33407
مقاله پژوهشی
Altered Serum Cytokine Profiles in Relapse Phase of Relapsing-Remitting Multiple Sclerosis
Forooz Peiravian
1
Hamid Rajaian
2
Afshin Samiei
3
Nasser Gholijani
4
Behrouz Gharesi-Fard
gharesifb@sums.ac.ir
5
Pooneh Mokaram
6
Abbas Rahimi-Jaberi
7
Eskandar Kamali Sarvestani
immunol2@sums.ac.ir
8
Department of Pharmacology and Toxicology, Shiraz University, Shiraz, Iran
Department of Pharmacology and Toxicology, Shiraz University, Shiraz, Iran
Autoimmune Diseases Research Center
Autoimmune Diseases Research Center
Infertility Research Center
Department of Biochemistry
Department of Neurology, Shiraz University of Medical Sciences, Shiraz, Iran
Autoimmune Diseases Research Center
Background: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system and cytokines may play a role in the development of MS lesions. Objective: To determine levels of different cytokines in patients with relapsing-remitting MS (RR-MS) compared to healthy controls. Methods: Profiles of pro-inflammatory, Th1-, Th2-, and Th17-related cytokines were compared by quantitative multiplexed ELISA-based chemiluminescent assay in 44 RR-MS and 44 healthy age- and sex-matched individuals from the same ethnicity. Results: Among pro-inflammatory cytokines, the levels of IL-6 (p=0.003), IL-8 (p=0.05) and TNF-α (p=0.002) were higher in patients than controls, though IL-4 and IL-10 as well as ΣTh2 cytokines were lower in patients (p=0.05, p=0.02 and p=0.05, respectively). After gender classification, the higher levels of IL-4 in male patients remained significant and IL-13 also showed significantly higher levels in male patients compared to male controls (p=0.003 and p=0.05, respectively). A significant negative correlation was detected between EDSS and IL-10 or ΣTh2 levels (p=0.005). In addition, IL-1α (r=0.4, p=0.05) and IFN-γ (r=0.35, p=0.05) were also directly correlated with EDSS in female patients. Conclusions: Patients with RR‑MS who are in the relapse clinical phase exhibit higher levels of pro-inflammatory cytokines and reduction in protective Th2-related cytokines.
https://iji.sums.ac.ir/article_33407_9c750effa4eb83814a0c9fb44c3e9264.pdf
Cytokines
Multiple Sclerosis
Th1
Th2
Th17
eng
Shiraz Institute for Cancer Research
Iranian Journal of Immunology
1735-1383
1735-367X
2016-09-01
13
3
197
203
33408
مقاله پژوهشی
Effect of TNF-α Blockade in Gingival Crevicular Fluid on Periodontal Condition of Patients with Rheumatoid Arthritis
Zeinab Kadkhoda
1
Aliakbar Amirzargar
amirzara@tums.ac.ir
2
Zahra Esmaili
3
Mahdi Vojdanian
4
Solmaz Akbari
soolmaz.akbari@gmail.com
5
Department of Periodontology, School of Dentistry
Molecular Immunology Research Center, Department of Immunology, School of Medicine
Dentistry Research Institute
Rheumatology Research Center, School of Medicine
Department of Periodontics, School of Dentistry, Tehran University of Medical Science, Tehran, Iran
Background: Periodontitis and rheumatoid arthritis (RA) share a number of clinical and pathologic features, one of which is the presence of the tumor necrosis factor alpha (TNF-α)-induced bone resorption that is involved in the pathogenesis of both. Objectives: To investigate the effect of TNF-α blockade on periodontal conditions in patients with active RA. Method: The periodontal statuses of 36 patients (26 females, 10 males) diagnosed with active RA were evaluated both before and after anti-TNF-α therapy. Gingival index, bleeding on probing (BOP), probing pocket depth (PPD), oral hygiene index (OHI), and levels of TNF-α in gingival crevicular fluid (GCF) were measured at the baseline and 6 weeks after the treatment. Wilcoxon signed ranked test was used for statistical analyses. Results: Based on OHI (p=0.860), the level of plaque control did not change during the study period, but there was a significant reduction in gingival inflammation based on the mean BOP (p=0.049) and GI (p=0.036) before and after 6 weeks of anti-TNF-α therapy. The mean PPD index did not significantly differ at the baseline and 6 weeks after treatment (p=0.126). Conclusion: Anti-TNF-α therapy might have a desirable effect on periodontal conditions and might reduce TNF-α level in GCF of patients with RA.
https://iji.sums.ac.ir/article_33408_4868e89e4ba865c5cb6b09c21ebfc588.pdf
Anti-TNF Alpha
Periodontal Diseases
Rheumatoid Arthritis
eng
Shiraz Institute for Cancer Research
Iranian Journal of Immunology
1735-1383
1735-367X
2016-09-01
13
3
204
219
33409
مقاله پژوهشی
Immunogenicity of 23-Valent Pneumococcal Vaccine in Children with Systemic Lupus Erythematosus
Soheila Alyasin
alyasins@sums.ac.ir
1
Marzieh Adab
marziehadab@yahoo.com
2
Asieh Hosseinpour
3
Reza Amin
aminr@sums.ac.ir
4
Maryam Babaei
5
Allergy Research Center, Department of Pediatrics, Division of Clinical Immunology and Allergy
Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Allergy Research Center, Department of Pediatrics, Division of Clinical Immunology and Allergy
Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease which is characterized by B-cell abnormality and auto-antibody generation. Since bacterial infections are the most important causes of mortality in these patients, pneumococcal vaccination is recommended for children with SLE. Objective: To investigate humoral immunity and specific-antibody formation in response to a 23-valent polysaccharide pneumococcal vaccination in SLE children and asthmatic control group. Method: The case and control groups consisted of 30 children with the mean age of 13 years who were matched by sex and age. Anti-pneumococcal antibody titers were determined using Enzyme-Linked Immunosorbent Assay (ELISA) before the vaccination with the 23-valent pneumococcal vaccine and 3 weeks later in both groups. Also the correlation between anti-pneumococcal antibody titer and different factors including age, sex, lupus activity, disease duration, medications, history of recurrent infections, and laboratory data were investigated. Results: Both groups showed significant increases in anti-pneumococcal antibody level after vaccination (p≤0.001). The increase in antibody level were almost the same in both groups (p≥0.05) such that 77.7% of SLE children and 86.2% of control children showed at least 2-fold increase in anti-pneumococcal antibody titer following immunization. Significant correlations were seen between the level of post-immunization anti-pneumococcal antibody with the age of children with SLE (p=0.02) and their age of disease onset (p=0.02). Conclusion: It is concluded that pneumococcal vaccination is generally immunogenic in children with SLE. However, a small group of patients show impaired response to the vaccine.
https://iji.sums.ac.ir/article_33409_372d363db30ad3f6ac3ac5e1e797c949.pdf
23-Valent Pneumococcal Vaccine
Anti-Pneumococcal Antibody
children
Immunogenicity
Systemic Lupus Erythematosus (SLE)
eng
Shiraz Institute for Cancer Research
Iranian Journal of Immunology
1735-1383
1735-367X
2016-09-01
13
3
220
228
33410
مقاله پژوهشی
The Immunostimulatory Effect of Lactic Acid Bacteria in a Rat Model
Murat Karamese
murat_karamese@hotmail.com
1
Hakan Aydin
2
Emin Sengul
3
Volkan Gelen
4
Cigdem Sevim
5
Duran Ustek
6
Emre Karakus
7
Department of Medical Microbiology, Faculty of Medicine, Kafkas University, Kars
Department of Virology, Faculty of Veterinary Medicine
Department of Physiology, Faculty of Veterinary Medicine, Ataturk University, Erzurum
Department of Physiology, Faculty of Veterinary Medicine, Kafkas University, Kars
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ataturk University, Erzurum
Department of Medical Genetics, Faculty of Medicine, Medipol University, Istanbul, Turkey
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ataturk University, Erzurum
Background: Probiotics are “live”, beneficial microbes that provide important health benefits in their hosts. There is significant interest in the modulation and regulation of the immune function by probiotics. Objective: To investigate the immunomodulatory effects of a probiotic mixture, including Lactobacillus and Bifidobacterium species, by detecting serum cytokine and immunoglobulin levels. Methods: The rats were randomly divided into 4 groups. The first group was “Control group” and other 3 groups were probiotic application groups who received different doses of probiotics. The probiotic mixture included 12 probiotic bacteria, mostly Lactobacillus and Bifidobacterium strains. Probiotic mixture was administered to rats for 12 consecutive days. TNF-α, TGF-β, IL-1-β, IL-6, and IL-10 levels as well as serum IgG and IgA concentrations were detected in the sera after 12 days. Results: Probiotics led to a decrease in the levels of TNF-α, IL-6 and TGF-β; however, they led to increase in the serum levels of IL-10, IgG and IgA. There were significant differences between control group and probiotic application groups (p<0.05). Conclusion: These data suggest that the commensal microbiota are important for stimulating both proinflammatory and regulatory responses in order to rapidly clear infections and minimize inflammation-associated tissue damage.
https://iji.sums.ac.ir/article_33410_4bed4d175068f24489cf7a5e48dacf15.pdf
Bifidobacterium
Cytokines
Immunomodulation
Lactobacillus
Probiotics
eng
Shiraz Institute for Cancer Research
Iranian Journal of Immunology
1735-1383
1735-367X
2016-09-01
13
3
229
236
33411
Maternal Serum and Cervicovaginal IL-6 in Patients with Symptoms of Preterm Labor
Parisa Yavari Kia
1
Behzad Baradaran
2
Mahnaz Shahnazi
3
Mohammad Asghari Jafarabadi
4
Vahid Khaze
5
Shakiba Pourasad Shahrak
sh.pourasad@yahoo.com
6
Department of Midwifery, Faculty of Nursing and Midwifery
Immunology Research Center
Department of Midwifery, Faculty of Nursing and Midwifer
Prevention Research Center
Immunology Research Center, Midwifery Student
Department of Midwifery, Faculty of Nursing and Midwifery, Tabriz University of Medical Sciences, Tabriz, Iran
Background: Preterm birth is a common problem in obstetrics. Objective: To measure maternal serum interlukin-6 in mothers with preterm uterine contractions and compare it with cervicovaginal interlukin-6 in the same women. Methods: In this cross-sectional study, we measured interlukin-6 in the sera and cervicovaginal fluids of 86 women with preterm uterine contractions. All participants had an intact membrane. Interlukin-6 was measured by using ELISA method. Statistical analysis was done using U-Mann Whitney, Chi-Square and Kendall’s tests. Results: The mean and median (Quartile25, Quartile75) of interlukin-6 in cervicovaginal fluid was higher than maternal serum interlukin-6. There was a statically significant difference in the median of interlukin-6 in sera and cervicovaginal fluid (P<0.0001). There was no significant correlation between serum and cervicovaginal interlukin-6 (r=0.048, p=0.548). Conclusion: There was no significant correlation between serum and cervicovaginal interlukin-6 (r=0.048, p=0.548). Conclusion: We found no relationship between serum interlukin-6 and preterm labor and the maternal serum Interlukin-6 does not seem to be a suitable biomarker for predicting preterm delivery.
https://iji.sums.ac.ir/article_33411_2152fcd0e41df5914df28588948f86ab.pdf
Cervicovaginal Fluid
Interlukin-6
Maternal Serum
Preterm Labor