Shiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138318220210601Immunoexpression of C4 Binding Protein in Oral Leukoplakia and Oral Squamous Cell Carcinoma951024765910.22034/iji.2021.87031.1782ENFatemehMashhadi-AbbasOral and Maxillofacial Pathology Department, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, IranDental Research Center, Research Institute of Dental School, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, IranMasoumeFayazi_BoroujeniOral and Maxillofacial Pathology Department, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran0000-0001-5059-1003AkramAlizadehCellular and molecular research center, basic health sciences institute, Shahrekord University of Medical Sciences, Shahrekord, Iran0000-0002-9956-4556MahshidNamdariCommunity Oral Health Department, Shahid Beheshti University of Medical Sciences, Tehran, IranSeyed AbbasMirzaeiSchool of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran0000-0003-0307-3750Journal Article20200626<strong>Background: </strong>The immune evasion of dysplastic cells plays an important role in suppressing the immune response and progression of malignancy. The role of the complement inhibitors in the development of oral epithelial dysplastic lesions and squamous cell carcinoma (SCC) is still unclear. <strong>Objective:</strong> This study aimed to assess the expression of C4 binding protein (C4BP) as a complement inhibitor in oral squamous cell carcinoma and leukoplakia. <strong>Methods:</strong> In this study, 94 samples were classified into four groups: leukoplakia with mild to moderate dysplasia, leukoplakia with severe dysplasia or carcinoma in situ, early invasive SCC, and invasive SCC. The expression of C4BP marker was evaluated by immunohistochemistry (IHC) and real-time PCR. The results were analyzed by the Kruskal-Wallis, Bonferroni adjusted Dunn’s multiple comparison, and one-way ANOVA tests. <strong>Results:</strong> The results of IHC revealed the expression patterns of C4BP in oral dysplasia and SCC, and indicated that the C4BP expression was not significantly different between different histopathological grades in epithelial cells and vessels (P=0.157 and P=0.123, respectively) but, it was significantly different in fibroblasts and lymphocytes (P=0.017 and P=0.043, respectively). The real-time PCR showed a significant correlation between the dysplasia grade and expression of C4BP (p <0.05). <strong>Conclusion:</strong> According to the results, C4BP is expressed in the cancerous tissue by the tumor cells and their surrounding stroma. In addition, upregulation of the C4BP gene as an inhibitor of the complement system is a possible strategy adopted by the tumor cells to evade the immune system.https://iji.sums.ac.ir/article_47659_7644a2c718b9ea88debd29db1c9e968f.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138318220210601VEGF-A, HGF and bFGF are involved in IL-17A-mediated migration and capillary-like vessel formation of vascular endothelial cells1031104766410.22034/iji.2021.91214.2059ENMuneoNumasakiLaboratory of Clinical Science and Biomedicine, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Japan0000-0001-7980-9854KoyuItoDepartment of Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, JapanJournal Article20210517<strong>Background:</strong> Interleukin (IL)-17A possesses biological activities to promote vascular endothelial cell migration and microvessel development. <strong>Objective:</strong> To clarify which angiogenic factors are involved in IL-17A-modified angiogenesis-related functions of vascular endothelial cell migration and microtube development or not. <strong>Methods:</strong> The potential contribution of various angiogenic stimulators to in vitro angiogenic activities of IL-17A was assessed with both modified Boyden Chemotaxicell chamber assay and in vitro angiogenesis assay. <strong>Results:</strong> The addition of a neutralizing antibody (Ab) for hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF)-A to the upper and lower compartments in a modified Boyden Chemotaxicell chamber significantly attenuated human dermal microvascular endothelial cell (HMVEC) migration elicited by IL-17A. Moreover, IL-17A-induced capillary-like microvessel development in human umbilical vein endothelial cell (HUVEC) and human dermal fibroblast (HDF) co-culture system was significantly impaired by a neutralizing Ab against HGF, bFGF, VEGF-A, cysteine-x-cysteine ligand 8 (CXCL8)/IL-8 or cysteine-x-cysteine (CXC) chemokine receptor (CXCR)-2. <strong>Conclusion:</strong> Our findings demonstrate the involvement of HGF, bFGF, VEGF-A and/or CXCL8/IL-8, to various degrees, in migration and microvessel development of vascular endothelial cells mediated by IL-17A.https://iji.sums.ac.ir/article_47664_96c4d28d753dbafe9004bd4e564f2c73.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138318220210601Diospyros peregrina fruit preparation mediated immunomodulation of lymphocytes isolated from the blood of breast cancer patients1111184765810.22034/iji.2021.85430.1710ENAhanaRoySRM Research Institute and Department of Biotechnology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603203, India0000-0002-8287-9746AitijhyaGhoshSRM Research Institute and Department of Biotechnology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603203, India0000-0002-9837-4208KasturiSinhaSRM Research Institute and Department of Biotechnology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603203, IndiaBasundharaMitraSRM Research Institute and Department of Biotechnology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603203, India0000-0001-5345-0740SudeshnaRakshitSRM Research Institute and Department of Biotechnology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603203, India0000-0002-7496-3155MelvinGeorgeDepartment of Clinical Pharmacology, SRM Medical College Hospital and Research Center, Kattankulathur, Tamil Nadu 603203, India0000-0001-7101-8513KoustavSarkarSRM Research Institute and Department of Biotechnology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603203, India0000-0002-0696-6688Journal Article20200229Background: Breast cancer is an uncontrolled growth of epithelial cells. The loss of BRCA1 activity due to mutation or down-regulation of gene expression promotes tumorigenesis and increases the risk of breast cancer. <br /> Objectives: Our aim was to pulsate lymphocytes of breast cancer patients and normal individuals, using Diospyros peregrina fruit preparation (DFP) to study the cancer protective immunity, and the signal transduction processes involved with it. We also investigated the role of DFP in the release of lymphocytic nitric oxide (NO), which is a key tumoricidal agent, known to regulate T-cell proliferation, cytokine production, cell signaling, and apoptosis. <br /> Methods: Using Ficoll-Hypaque gradient centrifugation, lymphocytes were isolated from the blood of 12 patients and 12 normal individuals. Cells were treated with or without DFP (2.5 µg/ml) for 48 hours. Both non-stimulated and stimulated cells were then subjected to MTT assay and NO release assay; following which qPCR was performed to estimate mRNA levels and percentage enrichment of certain genes.<br /> Results: DFP stimulates lymphocytic proliferation(p=0.0118) and release of NO(p=0.01) significantly.DFP also noticeablyenhances the expression of T helper (TH) cell 1 specific IFNG, IL12, TBX21 and signal transducer and activator of transcription 1 (STAT1) genes. DFP treatment significantly increases tumor protective immunity by decreasing the expression levels of TH2 network specific GATA3 and IL4 genes but increasing the expression levels of TH1 network specific IFNG, IL12, TBX21 and STAT1 genes. <br /> Conclusion: DFP increases the expression levels TH1 specific network genes which in turn help in evoking tumor protective immunity.https://iji.sums.ac.ir/article_47658_6d3edbdd7c3f2ab2d47df3eeb3a805b8.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138318220210601Effect of bortezomib regimens and daratumumab monotherapy on cellular immunity in multiple myeloma patients1191294766010.22034/iji.2021.87547.1812ENAshrafKakooBiology Department, College of Science, Salahaddin University, Erbil, Iraq0000-0002-7722-5289TabanRasheedBiology Department, College of Science, Salahaddin University, Erbil, Iraq0000-0001-9586-7843MustafaAl-AttarBiology Department, College of Science, Salahaddin University, Erbil, Iraq0000-0002-2106-130XJournal Article20200806<strong>Background: </strong>Treatment with Bortezomib (a proteasome inhibitor) and Daratumumab (DARA, a monoclonal anti CD38 antibody) are effective in patients with multiple myeloma (MM). However, these drugs impair cellular immunity, which may render the patients more prone to infection. <strong>Objective</strong>: To investigate the effect of Bortezomib-based regimens and Daratumumab monotherapy on the lymphocyte subpopulations in MM patients. <strong>Methods: </strong>Peripheral blood samples were collected from 32 patients, including 29 newly diagnosed who treated with bortezomib regimens and 3 patients with relapsed and refractory MM treated with Daratumumab as monotherapy. The immunophenotypic analysis was performed by flow cytometry at baseline and during the third cycle of Bortezomib regimen and fourth week of Daratumumab treatment. <strong>Results:</strong> In the third cycle of Bortezomib, there was a significant decrease in CD3<sup>+</sup> T cells, CD<sup>+</sup>4 T cells, memory T cells, and natural killer cells (NK cells). However, CD8<sup>+</sup> T cells increased dramatically, followed by a significant reduction in the CD4/CD8 ratio. On the other hand, Daratumumab led to an increase in the T cell population after four weeks of treatment, with a significant increase in CD3<sup>+</sup> T cells as well as CD4<sup>+</sup> T cells, while NK cells were dramatically depleted in all patients. <strong>Conclusion:</strong> Bortezomib had a negative influence on subsets of T cells, while Daratumumab positively affected T cells subsets. In both treatments, NK cells decreased significantly. These results suggested that DARA is more specific to target myeloma cells than Bortezomib. Also, DARA expanded T cells especially CD3<sup>+</sup> T cells and CD4<sup>+</sup> T cells.https://iji.sums.ac.ir/article_47660_4170419ab063f5be3b93901a6ae1bba9.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138318220210601IL-17 Genetic Variations Increase the Risk of Cirrhotic/Hepatocellular Carcinoma in Patients with Hepatitis B Virus Infection.1301404766110.22034/iji.2021.88020.1852ENAbolfazlGheshlaghiDepartment of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranMohammad RezaHaghshenasShiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran0000-0001-8228-9888Ali RezaSafarpourGastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IranSeyed YounesHossiniDepartment of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranSeyed AliMalekhosseiniTransplant Research Center, Shiraz University of Medical Sciences, Shiraz, IranMohammad RezaFattahiGastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IranJamalSarvariDepartment of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran0000-0002-2259-0836Journal Article20201002<strong>Background:</strong> Genetic variation in immune regulatory genes might influence the HBV infection outcome. <strong>Objective:</strong> This study aimed to determinethe association of IL-17A rs2275913 (G197A), IL-17F rs763780 (A7488G), and IL-23R rs10889677 (C2370A) gene polymorphisms, as well as the emerged haplotypes in the individual infected by HBV and to investigate their association with the infection outcome. <strong>Materials and Methods:</strong> 300 chronic HBV infections with Cirrhotic/Hepatocellular carcinoma (C/HCC), chronic active (CA), and asymptomatic carrier (AC) and 38 individuals whose infection was spontaneously cleared (SC) were enrolled. Genomic DNA was extracted, and IL-17A/F and IL-23R genotyping were performed by using the PCR-RFLP method. <strong>Results:</strong> Out of 338 subjects, 238 and 100 were respectively male and /female with a mean age of 47.61±13.41. The frequency of GA genotype (p=0.01) and A alleles (p=0.001) of IL-17A rs2275913 (G197A), as well as the frequency of AA genotype (p=0.014) and A alleles (p=0.018) of IL-17F rs763780 (A7488G) gene locus, was found to be significantly higher in the C/HCC than CA and AC groups. Furthermore, the frequency of GA and AG haplotype in CA individuals was higher than those with C/HCC and AC (p=0.003). Also, the GG haplotype was higher in AC individuals than those with C/HCC (P=0.022), and the AA haplotype was higher in C/HCC individuals than the CA patients (P=0.001). <strong>Conclusion:</strong> Our findings suggest that A allele and GA genotype at IL-17A rs2275913 (G197A), as well as A allele and AA genotype at IL-17F rs763780 (A7488G) locus, might be associated with increased risk of C/HCC among patients with hepatitis B virus infection.https://iji.sums.ac.ir/article_47661_a95dd4f398c818175248ccef3daa56f2.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138318220210601Recombinant Production and One Step Purification of IL-1Ra in Escherichia coli and Evaluation its IL-1 Antagonizing Efficacy1411494766310.22034/iji.2021.89103.1929ENRoyaAdelniaDepartment of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, IranFatemehShafieePharmaceutical Science Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran0000-0001-6484-1931Journal Article20201124Background: Anakinra (Kineret®), an IL-1 receptor antagonist, is the first FDA approved biologic drug for antagonizing IL-1 effects in patients with Rheumatoid arthritis. Notably, the less expensive production of this drug might help reduce the final therapeutic costs. Objectives: This study aimed to evaluate the possibility of producing biologically active recombinant IL-1Ra by a single step purification procedure mediated by a self-cleavable intein. Methods: Soluble expression of the rIL-1Ra was performed in E. coli BL21 (DE3) in fusion to intein1 of pTWIN-1 vector and its cleavage induction using an elution buffer (pH 6.8) at room temperature. Evaluation of the antagonizing efficacy of this protein in various concentrations, was performed on A375 and HEK293 cells treated by a constant concentration of IL-1β (2ng/mL). Results: IPTG induction of E. coli BL21 (DE3) transformed with the recombinant pTWIN-1, revealed a band approximately in 45 kDa, which is related to the intein1-rIL-1Ra fusion protein in the SDS-PAGE. Moreover, protein purification was confirmed by observing a band in 18 kDa. Finally, the percentage of inhibition effects of rIL-1Ra and Kineret® against IL-1β was not statistically significant in IL-1-responsive A375 cells. The inhibition percentage was calculated as 86% in cells treated with 15µg/mL of rIL-1Ra, which it was 96% for the inhibitory effects of the standard drug. Conclusion: In this study, biologically active soluble rIL1-Ra was successfully produced with high purity through a one-step procedure. This method can reduce the cost and time of production for this protein and might be applicable for producing other biologics.https://iji.sums.ac.ir/article_47663_7cb17c589536a531871964cf32a22a4f.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138318220210601Camrelizumab plus zoledronic acid showed sustained efficacy in a patient with cranial and spinal metastases from lung adenocarcinoma1501574766510.22034/iji.2021.87760.1828ENChuZhangDepartment of Thoracic Surgery, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, P.R.China0000-0001-5860-8500GuangmaoYuDepartment of Thoracic Surgery, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, P.R.China0000-0002-1737-9243MiaoZhangDepartment of Thoracic Oncology, Xuzhou Central Hospital, Xuzhou, P.R.China0000-0001-7431-5986WenbinWuDepartment of Thoracic Oncology, Xuzhou Central Hospital, Xuzhou, P.R.China0000-0002-8183-1687Journal Article20200813The role of anti-programmed cell death protein-1 (PD-1) antibody camrelizumab in brain metastases (BMs) from lung adenocarcinoma is uncertain. Herein, for the first time, we report the efficacy of camrelizumab in a patient with chemotherapy-refractory BMs from lung adenocarcinoma. A 49-year-old male non-smoker was admitted with cough and back pain. Primary lung adenocarcinoma with brain and spinal metastases was diagnosed. The specimen from CT-guided lung biopsy showed positive expression of PD-L1 (~20%). The BMs were enlarged after first-line intravenous pemetrexed/cisplatin and zoledronic acid; whereas second-line camrelizumab demonstrated impressive complete remission of the BMs. The intracranial progression-free survival and overall survival of the patient since immunotherapy were more than 12 months and 20 months, respectively. In addition, we searched PubMed for relevant studies from inception to May 2020, and a total of 23 reports enrolling 1187 patients also indicated the promising efficacy of immunotherapy for BMs from lung cancer. However, more and better evidence are still needed before a definite conclusion could be drawn.https://iji.sums.ac.ir/article_47665_95051d4b7645ea6bea3a8049ed7a3857.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138318220210601High level of IgG4 in a patient with Extensive pulmonary involvement1581624766210.22034/iji.2021.88789.1907ENMohammad HasanBemanianDepartment of Allergy and Clinical Immunology, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran0000000309984651SimaBahramiDepartment of Allergy and Clinical Immunology, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran0000-0002-5544-6961SabaArshiDepartment of Allergy and Clinical Immunology, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, IranAfshinRezaeifarDepartment of Allergy and Clinical Immunology, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, IranMohammadNabaviDepartment of Allergy and Clinical Immunology, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, IranMortezaFallahpourDepartment of Allergy and Clinical Immunology, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran0000-0002-5148-8312SimaShokriDepartment of Allergy and Clinical Immunology, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran0000-0002-2176-3934Journal Article20201103Immunoglobulin G4-Related Disease (IgG4-RD) is a systemic fibro-inflammatory disease that has been proposed as a separate entity since thebeginning of this century. The disease is often manifested by increasedserum IgG4 levels and certain histopathological manifestations. The patientmentioned in this article is a 29-year-old man from Tajikistan, who has had achronic cough since the beginning of 2018 without a previous history of thedisease. At first, he was diagnosed with pneumonia for a long time and thenunderwent a lung biopsy due to exacerbation of symptoms and the spreadof lung lesions in radiology but no abnormalities were found in theseevaluations. The patient traveled to Iran to continue his treatment. He wasre-evaluated and then the previous samples taken from the patient's lungtissue were re-examined. There were key findings in favor of diagnosingIgG4 RD. Evaluations did not confirm the involvement of other organs. Hewas first treated with steroids and due to recurrence of symptoms, he wastreated with rituximab once which was significantly effective in improving thepatient's clinical symptoms. In general, it can be concluded that thediagnosis of IgG4-RD is very challenging and if it has not been diagnosedand treated in time, it can lead to irreversible fibrosis and permanent loss offunction of the involved organ.https://iji.sums.ac.ir/article_47662_194ad27f3492c7a09255263eb6ae6874.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138318220210601Differential diagnosis from isolated lymphoid extramedullary blast crisis from secondary non-Hodgkin lymphoma in chronic myelogenous leukemia: a case report and literature review1631694765710.22034/iji.2021.84496.1661ENTingtingWangDepartment of International Medical Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaLiFuDepartment of International Medical Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaNaWeiDepartment of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaXiaogeZhouDepartment of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaXiaodanZhengDepartment of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaLiLiDepartment of International Medical Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaZhaoWangDepartment of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China0000-0002-1819-8532Journal Article20191212Case: Extramedullary blast crisis (EBC) is a special kind of blast crisis of chronic myelogenous leukemia (CML). It is more likely to be misdiagnosed as lymphoma when EBC cells are of lymphoid cell lineage and lymphadenopathy is the only symptom before the final diagnosis. In this study, we presented a patient with an unusual presentation of CML transformation as a rapid growth of generalized lymphadenopathy that appeared 5 months after the initial diagnosis<br />of CML. The patient underwent the left supraclavicular lymph node biopsy and repeat bone marrow aspiration. The revealed CD3+, terminal deoxynucleotidyl transferase (TdT)+, CD5+, CD23+, myeloperoxidase (MPO)-, CD20-, cyclin D1-, CD10-, which was consistent with the diagnosis of T-cell lymphoblastic lymphoma (T-LBL). Fluorescence in situ hybridization (FISH) verified the BCR-ABL rearrangement, and T-cell EBC of CML was finally diagnosed. Our report suggested that the FISH was necessary to distinguish isolated lymphoid extramedullary blast crisis from secondary NHL in CML.https://iji.sums.ac.ir/article_47657_399f488c2bb3bbf7e91d813c6e1599b8.pdf