Original Article
Ali Ariafar; Zahra Mansourabadi; Hojat Alipoor; Zahra Faghih
Abstract
Background: Gamma-delta (γδ) T cells are a distinct subset of T cells with a receptor composed of γ and δ chains. Their ability to directly recognize stress-induced molecules and non-peptide antigens expressed by cancer cells, along with their capacity to produce cytokines and ...
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Background: Gamma-delta (γδ) T cells are a distinct subset of T cells with a receptor composed of γ and δ chains. Their ability to directly recognize stress-induced molecules and non-peptide antigens expressed by cancer cells, along with their capacity to produce cytokines and interact with other immune cells, makes them potentially significant contributors to immune-based treatments.
Objective: To investigate the presence and frequency of Tγδ cells in tumor-draining lymph nodes of patients with bladder cancer (BC), and to assess their association with prognostic parameters.
Methods: Forty-nine fresh tumor-draining lymph nodes from untreated patients with BC were minced to obtain single cells. The cells were surface-stained with anti-CD3, anti-TCRγδ, and anti-HLA-DR antibodies, then acquired on a four-color FACSCalibur flow cytometer, and analyzed by FlowJo software.
Results: On average, 2.07% ± 1.99% of CD3+ lymphocytes in regional nodes of BC exhibited a γδ T phenotype. A considerable percentage of these cells (37.90% ± 24.42%) expressed HLA-DR. Statistical analysis revealed that while the frequency of γδ T cells showed no variation among patients with different prognoses, the HLA-DR+ subset was higher in T4 patients than in T2 patients (p=0.031). These cells also tended to be increased in stage III compared to stage II (p=0.077).
Conclusion: The data collectively indicated an association of HLA-DR expressing γδ T cells with prognostic factors related to tumor progression (higher T-group and stage), suggesting their potential involvement in disease progression. However, future research, including longitudinal studies with larger cohorts, needs to validate these findings and elucidate the functional roles of γδ T cells in the immune response against BC.
Original Article
Marlen Vitales-Noyola; Diana Lorena Alvarado-Hernández; Raquel Sánchez-Gutiérrez; Berenice Hernández-Castro; Larisa González-Baranda; Sofía Bernal-Siva; Andreu Comas-García; Carmen Sánchez-Torres; Roberto González-Amaro
Abstract
Background: Clinical manifestations SARS-CoV-2 infection are variable, ranging from asymptomatic to pneumonia, and different serious complications. It has been observed that some populations exhibit an enhanced risk for severe disease and death, compared to other ethnical groups.Objective: To evaluate ...
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Background: Clinical manifestations SARS-CoV-2 infection are variable, ranging from asymptomatic to pneumonia, and different serious complications. It has been observed that some populations exhibit an enhanced risk for severe disease and death, compared to other ethnical groups.Objective: To evaluate two parameters of the innate immune system, which have a relevant role in viral immunity.Methods: In samples of peripheral blood from sixteen patients with severe COVID-19, ten with asymptomatic-mild disease, and fifteen healthy controls, the numbers of NK and NKT cells, the expression of different NK cell receptors and the serum levels of pro-inflammatory cytokines were analyzed.Results: We found that patients with severe COVID-19 showed significant lower levels of both CD56dim and CD56bright NK cells compared to patients with mild disease or healthy subjects. Furthermore, an abnormal expression of the natural cytotoxicity receptors NKp30, NKp44 and NKp46 was observed in severe COVID-19 patients. Likewise, NK cells from these patients also showed significant differences in the expression of several killer immunoglobulin-like receptors (KIR’s), in the two main cell subsets (CD56bright, CD56dim), compared to controls or patients with mild disease. Moreover, patients with severe COVID-19 showed lower levels of NKT cells (defined as CD3+CD56+) and increased serum concentrations of IL-6 and IL-8.Conclusion: We consider that the abnormalities in NK and NKT cells observed in patients with severe COVID-19 might have a relevant role in the outcome of this infection in some population groups.
Original Article
Rouhollah Hemmati Bushehri; Mahmoud Reza Jaafari; Ghasem Mosayebi; Ali Ghazavi; Ali Ganji
Abstract
Background: Rosemary (Ros) is a member of the Lamiaceae family known for its antitumor properties. However, its low water solubility and impaired bioavailability are limiting factors when using rosemary extract. Liposomes are synthetic vesicles that offer permeability, improved bioavailability, and lack ...
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Background: Rosemary (Ros) is a member of the Lamiaceae family known for its antitumor properties. However, its low water solubility and impaired bioavailability are limiting factors when using rosemary extract. Liposomes are synthetic vesicles that offer permeability, improved bioavailability, and lack of immunogenicity and toxicity, making them ideal for delivering various drugs.Objective: To prepare liposomes (HSPC/Chol/mPEG2000-DSPE) containing rosemary alcoholic extract (LipRos) and evaluate its antitumor properties in a mouse model of colorectal cancer (CRC).Methods: LipRos were prepared and characterized. CRC was induced in Balb/c mice by subcutaneous injection of C26 cells, and tumor size was monitored continuously. The MTT assay was performed to evaluate cytotoxicity, and liver and kidney function tests were conducted to assess safety. The expression of the pro-apoptotic gene B-cell-lymphoma-2 (Bcl-2), the anti-apoptotic gene Bcl-2-associated-X-protein (Bax), and the expression of cytokines Tumor-necrosis-factor-alpha (TNF-α), Transforming-growth-factor-beta (TGF-β), and Interferon-gamma (IFN-γ) were investigated using real-time PCR. Flow cytometry was used to evaluate the count of cytotoxic (CTL) and regulatory T lymphocytes (Tregs) in spleen and tumor tissue.Results: The results showed that the size of liposomal formulations and their encapsulation efficiency were 113.4 nm and 85%, respectively. The MTT assay demonstrated insignificant cytotoxicity of LipRos on splenocytes, and the tumor size was significantly reduced in the LipRos group (P=0.00045). LipRos also significantly decreased Bcl-2 gene expression (P=0.0086), increased Bax and IFN-γ gene expression (P=0.031), and enhanced the infiltration of CTLs in tumor tissue (P=0.023).Conclusions: This study showed that PEGylated (Poly-Ethylene-Glycol) liposomes containing rosemary extract exhibit an antitumor effect on C26 colorectal cancer cells through multiple mechanisms. These findings can be utilized in future studies.
Original Article
Maryam Teimouri; Ahad Muhammadnejad; Mir Saeed Yekaninejad; Alireza Razavi; Gholam Ali Kardar
Abstract
Background: Interleukin-2 (IL-2) is a well-known cytokine that plays a crucial role in stimulating immune cells, including natural killer (NK) cells and cytotoxic T cells. It has been studied as an immunotherapy for a variety of diseases, including cancer. However, due to its short serum half-life, high ...
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Background: Interleukin-2 (IL-2) is a well-known cytokine that plays a crucial role in stimulating immune cells, including natural killer (NK) cells and cytotoxic T cells. It has been studied as an immunotherapy for a variety of diseases, including cancer. However, due to its short serum half-life, high doses of IL-2 are required which can result in systemic toxicities like capillary leak syndrome.Objective: To demonstrate the enhanced antitumor efficacy of Albumin Binding Domain-conjugated IL-2 (ABD-IL-2) at a lower dose compared to IL-2.Methods: IL-2 and ABD-IL-2 were purified using Ni-NTA resin with a histidine sequence added to their C-terminal region for purification purpose. Peripheral blood lymphocytes were stimulated with IL-2 and ABD-IL-2 to assess their function. 4T1 cells were injected into BALB/c mice to establish a breast cancer model with metastasis evaluated in the lungs.Results: Both recombinant proteins significantly stimulated T lymphocyte proliferation compared to the negative control (P=0.000, P=0.001). Administration of both proteins reduced the size of isolated tumors in the breast cancer mouse model. The control group had more nodules and larger lung metastatic centers (P=0.000). Metastasis to secondary lymphoid organs occurred only in the control group.Conclusion: By using ABD-IL-2 at a one-third concentration compared to IL-2, we aimed to reduce administration toxicity associated with high doses of IL-2 in immunotherapy. This approach shows potential for improving IL-2-based treatments while minimizing adverse effects.
Original Article
Hui-Jun Yu; Qi Wan; Li Tan; Xing-Yu Lv
Abstract
Background: Patients with thin endometrium undergoing frozen-thawed embryo transfer often encounter challenges with pregnancy outcomes. Enhancing endometrial receptivity and immune tolerance may improve these outcomes.Objective: To investigate the effects of intrauterine perfusion of granulocyte colony-stimulating ...
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Background: Patients with thin endometrium undergoing frozen-thawed embryo transfer often encounter challenges with pregnancy outcomes. Enhancing endometrial receptivity and immune tolerance may improve these outcomes.Objective: To investigate the effects of intrauterine perfusion of granulocyte colony-stimulating factor (G-CSF) and human chorionic gonadotropin (HCG) on regulatory T cells (Tregs) and pregnancy outcomes in patients with thin endometrium undergoing frozen-thawed embryo transfer.Methods: 150 patients with thin endometrium were randomly assigned to three groups: a control group that received no intervention, an HCG group, and a G-CSF group. The effectiveness of the treatments was assessed by comparing uterine parameters, Treg levels, and pregnancy outcomes across the groups.Results: The HCG and G-CSF groups exhibited significant improvements compared to the control group, including increased endometrial thickness, enhanced blood flow, higher expression of endometrial receptivity markers (integrin αvβ3, osteopontin), and elevated Treg levels. Notably, the G-CSF group demonstrated even greater enhancements compared to the HCG group, with significantly higher endometrial thickness, better blood flow, increased receptivity markers, and elevated Treg levels. Additionally, the G-CSF group achieved significantly higher biochemical and clinical pregnancy rates compared to both the HCG and control groups. This highlights the potential of G-CSF in improving pregnancy outcomes for patients with a thin endometrium.Conclusion: The intrauterine perfusion of G-CSF significantly enhanced pregnancy outcomes in patients with thin endometrium by improving endometrial blood flow, immune tolerance, thickness, Treg induction, and embryo implantation. These findings suggest that G-CSF could be a promising therapeutic option for this patient population.
Original Article
Anil Demir; Husnu Sevik; Mert Guler; Furkan Turkoglu; Coskun Cakir; Mert Mahsuni Sevinc; Erdem Kinaci; Ufuk Oguz Idiz
Abstract
Background: Breast cancer is the primary contributor to cancer-related deaths in women. Cytokines have been linked to various cancers, and both benign and malignant breast diseases are associated with inflammation. However, there is limited understanding of how the immune system's cytokine response varies ...
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Background: Breast cancer is the primary contributor to cancer-related deaths in women. Cytokines have been linked to various cancers, and both benign and malignant breast diseases are associated with inflammation. However, there is limited understanding of how the immune system's cytokine response varies across different breast cancer subtypes.Objective: This study seeks to evaluate cytokine levels in breast cancer patients based on their subtypes and to explore the potential role of these cytokines in treatment. Methods: Patients with stage 1-2 breast cancer and healthy volunteers were included. The breast cancer patients were classified as luminal A, luminal B, and triple negative according to ER, PR, HER2 receptor status, and Ki67 score of trucut biopsy results. Multiplex assay and flow cytometry were used to quantify the concentrations of IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p (p70), IL-17A, IL-18, IL-23, and IL-33 in serum samples collected from all participants. Age, menopause status, and hematologic parameters were also compared between groups.Results: The study included 19 luminal A, 20 luminal B, 18 triple-negative patients and 21 healthy volunteers. TNF-α, IL-6, IL-8, IL-10, IL-12p (p70), IL-18, and IL-23 cytokines were significantly higher in breast cancer patients compared to healthy volunteers. Significant differences in IFN-γ, IL-6, IL-8, IL-10, IL-12p (p70), IL-17A, IL-18, and IL-23 were observed between subtypes, with triple-negative patients exhibiting lower cytokine levels, except for MCP-1.Conclusion: The reduced cytokine levels in triple-negative breast cancer suggest weaker immunogenicity and more aggressive tumor progression due to an inadequate immune response.
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