Review Article
Abdolkarim Sheikhi; Abdollah Jafarzadeh; Parviz Kokhaei; Mohammad Hojjat-Farsangi
Volume 13, Issue 3 , September 2016, Pages 148-166
Abstract
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 ...
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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.
Original Article
Hamideh Mesali; Abolghasem Ajami; Hadi Hussein-Nattaj; Alireza Rafiei; Zeinab Rajabian; Hossein Asgarian-Omran; Vahid Hosseini; Tarang Taghvaei; Mohsen Tehrani
Volume 13, Issue 3 , September 2016, Pages 167-177
Abstract
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 ...
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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.
Original Article
Nazanin Nazari; Shirin Farjadian
Volume 13, Issue 3 , September 2016, Pages 178-185
Abstract
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: ...
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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.
Original Article
Forooz Peiravian; Hamid Rajaian; Afshin Samiei; Nasser Gholijani; Behrouz Gharesi-Fard; Pooneh Mokaram; Abbas Rahimi-Jaberi; Eskandar Kamali Sarvestani
Volume 13, Issue 3 , September 2016, Pages 186-196
Abstract
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 ...
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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.
Original Article
Zeinab Kadkhoda; Aliakbar Amirzargar; Zahra Esmaili; Mahdi Vojdanian; Solmaz Akbari
Volume 13, Issue 3 , September 2016, Pages 197-203
Abstract
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 ...
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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.
Original Article
Soheila Alyasin; Marzieh Adab; Asieh Hosseinpour; Reza Amin; Maryam Babaei
Volume 13, Issue 3 , September 2016, Pages 204-219
Abstract
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 ...
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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.
Original Article
Murat Karamese; Hakan Aydin; Emin Sengul; Volkan Gelen; Cigdem Sevim; Duran Ustek; Emre Karakus
Volume 13, Issue 3 , September 2016, Pages 220-228
Abstract
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, ...
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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.
Short Paper
Parisa Yavari Kia; Behzad Baradaran; Mahnaz Shahnazi; Mohammad Asghari Jafarabadi; Vahid Khaze; Shakiba Pourasad Shahrak
Volume 13, Issue 3 , September 2016, Pages 229-236
Abstract
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 ...
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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.
