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Anticancer immunotherapies with a dendritic Cell (DC) basis are becoming more popular. However, it has been suggested that the tumor's immunosuppressive mechanisms, such as inhibitory immunological checkpoint molecules, reduce the effectiveness of anticancer immunogenicity mediated by DC. Thus, overcoming immune checkpoints and inducing effective antigen-specific T-cell responses uniquely produced with malignant cells represent the key challenges. Among the inhibitory immune checkpoints, DCs' ability to mature and present antigens is decreased by CTLA-4 expression. Consequently, we hypothesized that by expressing CTLA-4 cells on DCs, the T cells' activation against tumor antigens would be suppressed when confronted with these antigens presented by DCs. In this research, by loading cell lysate of breast cancer (BC) on DCs and the other hand by inhibiting the induction of CTLA-4 using small interfering RNA (siRNA), we assessed the functional activities and phenotypes of DCs, and also the responses associated with T-cells following co-culture DC/T cell. Our research has shown that the suppression of CTLA-4 enhanced the stimulating capabilities of DCs. Additionally, CTLA-4-suppressed BC cell lysate-loaded DCs produced more IL-4 and IFN-ϒ and increased T cell induction in contrast to DCs without CTLA-4 suppression. Together, our data point to CTLA-4-suppressed DCs loaded with BC cell lysate as a potentially effective treatment method. However, further research is required before employing this method in therapeutic contexts.

The new coronavirus was first reported in China and caused a widespread global outbreak of pneumonia that spread rapidly across this country and many other countries. Acute kidney injury is one of the important complications of COVID-19, which has been shown in some cases. Exploring the diagnostic features of biomarkers of kidney function in COVID-19 patients may lead to better patient management. We collected laboratory data from 206 people with confirmed COVID-19 disease and evaluated their renal biomarkers, Blood Urea Nitrogen (BUN), and creatinine. The age range of the patients was almost 62 years old. The mean age in the dead patients and recovered patients was 71 and 54 years old, respectively. The average LDH value was 755 U/L, and creatine phosphokinase (CPK) was 267 U/L in the patients. The average BUN was 59.1 U/L, and creatinine was 1.5 U/L in COVID-2019 patients. Among all 193 patients, laboratory results revealed that 163 (85.4 %) patients had an elevated BUN level. Based on creatinine levels for total patients, laboratory results revealed that 49 (25.4 %) patients had an elevated value. The average BUN value in dead patients was 85 mg/dL, while in recovered patients was 40.5 mg/dL (P

Background: Gastric cancer, ranked as the fifth most common cancer worldwide, presents multiple treatment challenges. These obstacles often arise due to cancer stem cells, which are associated with recurrence, metastasis, and drug resistance. While dendritic cell (DC)-based immunotherapy has shown promise as a therapeutic strategy, its efficacy can be limited by the tumor microenvironment and certain inhibitory immune checkpoint molecules, such as B7H7. SiRNA-medicated knockdown of B7H7 in tumor cell lysate-pulsed DCs can increase cytokine secretion and autologous T lymphocyte expansion. This study aimed to evaluate the impact of B7H7 suppression in gastric cancer cell lysate-pulsed DCs on the stimulatory potential of autologous CD3+ T lymphocytes. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated and monocytes were obtained; then, they were differentiated to immature DCs (iDCs) by GM-CSF and IL-4. Tumor cell lysates from human gastric cancer cell lines were harvested, and iDCs were transformed into mature DCs (mDCs) by stimulating iDCs with tumor cell lysate and lipopolysaccharide. B7H7-siRNA was delivered into mDCs using electroporation, and gene silencing efficiency was assessed. The phenotypic characteristics of iDCs, mDCs, and B7H7-silenced mDCs were evaluated using specific surface markers, an inverted light microscope, and flow cytometry. CD3+ T cells were isolated via magnetically activated cell sorting. They were labeled with CFSE dye and co-cultured with mDCs and B7H7-silenced mDCs to evaluate their ability to induce T-cell proliferation. T-cell proliferation was assessed using flow cytometry. The concentration of TGF-β, IL-4, and IFN-γ secreted from CD3+ T cells in the co-cultured supernatant was evaluated to investigate the cytokine secretory activity of the cells. Results: Transfection of B7H7 siRNA into mDCs was performed in optimal conditions, and the siRNA transfection effectively reduced B7H7 mRNA expression in a dose-dependent manner. SiRNA-mediated B7H7 knockdown in mDCs enhanced maturation and activation of the DCs, as demonstrated by an increased surface expression of CD11c, CD86, and CD40. Co-culture experiments revealed that B7H7-silenced mDCs had more capacity to induce T cell proliferation compared to non-transfected mDCs. The cytokine production patterns of T cells were also altered. Upon examining the levels of TGF-β, IL-4, and IFN-γ released by CD3+ T cells in the co-culture supernatant, we found that silencing B7H7 in mDCs resulted in a rise in IL-4 secretion and a reduction in TGF-β levels compared to mDCs that were not transfected. Conclusions: The study found that suppressing B7H7 expression in DCs significantly enhances their maturation and stimulatory activity when exposed to gastric cancer cell lysate. These B7H7-silenced DCs can substantially increase cytokine production and promote co-cultured T-cell expansion. Consequently, inhibiting B7H7 in DCs may offer a practical strategy to enhance the ability of DCs to initiate T lymphocyte responses and improve the effectiveness of DC-based cell therapy for cancer patients.

Dendritic cell (DC)-based immunotherapy has increased interest among anti-cancer immunotherapies. Nevertheless, the immunosuppressive mechanisms in the tumor milieu, e.g., inhibitory immune checkpoint molecules, have been implicated in diminishing the efficacy of DC-mediated anti-tumoral immune responses. Therefore, the main challenge is to overcome inhibitory immune checkpoint molecules and provoke efficient T-cell responses to antigens specifically expressed by cancerous cells. Among the inhibitory immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression on DCs diminishes their maturation and antigen presentation capability. Accordingly, we hypothesized that the expression of CTLA-4 on DCs inhibits the T cell-mediated anti-tumoral responses generated following the presentation of tumor antigens by DCs to T lymphocytes. In this study, we loaded colorectal cancer (CRC) cell lysate on DCs and inhibited the expression of CTLA-4 by small interfering RNA (siRNA) in them to investigate the DCs’ functional and phenotypical features, and T-cell mediated responses following DC/T cell co-culture. Our results demonstrated that blockade of CTLA-4 could promote stimulatory properties of DCs. In addition, CTLA-4 silenced CRC cell lysate-loaded DCs compared to the DCs without CTLA-4 silencing resulted in augmented T cell proliferation and cytokine production, i.e., IFN-γ and IL-4. Taken together, our findings suggest CTLA-4 silenced CRC cell lysate-loaded DCs as a promising therapeutic approach however further studies are needed before this strategy can be used in clinical practice.

Background: A new type of beta-coronavirus, named acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused coronavirus disease 2019 (COVID-19). Although COVID-19 is primarily associated with respiratory symptoms, cardiovascular complications can also occur. Herein, we aimed to evaluate whether the serum levels of enzymes related to cardiac injury, lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB), may associate with the mortality of COVID-19 patients to provide new insights to enhance clinical care. Methods: Based on hospital information systems (HIS) and patient records, we have retrospectively extracted laboratory findings of 159 patients with confirmed COVID-19 disease. The data of LDH and CK-MB of patients were defined as the day onset when the patients were admitted to the hospital. Results: The average age of all patients was almost 62 years old; the mean age in dead patients and recovered patients were 70 and 55 years old, respectively. The average aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine phosphokinase (CPK) values were 91.74, 66.20 U/L, and 268.24 U/L, respectively in all patients. The average LDH was 758.69 U/L, and CK-MB was 39.87 U/L in all of the COVID-19 patients. Among all 140 patients, laboratory results revealed that 121 (86.4%) patients had an elevated LDH level. In total, for 159 patients, the results indicated that 114 (71.69%) patients had an elevated CK-MB value. The average LDH value in dead patients was 1012.22 U/L, while in recovered patients was 545.20 U/L (P

Background: Interleukin (IL)-6, one of the inflammatory mediators involved in severe cases of coronavirus disease-19 (COVID-19), has been implicated in the pathogenesis of this disease. Extracorporeal blood purification has been suggested as one of the therapeutic strategies for COVID-19 patients, due to its favorable effect on the removal of inflammatory cytokines. Here, we investigated the impact of hemoperfusion (HP), a type of extracorporeal blood purification, in serum IL-6 levels and disease severity in COVID-19 patients. Methods: 35 patients with severe COVID-19 were enrolled in this study at the Imam-Reza Hospital, Tabriz University of Medical Sciences, between April 2020 and June 2020. The HA330 disposable HP cartridge was utilized (Jafron Biomedical Company, China). After a hemodialysis catheter was placed, patients underwent HP for at least three days in a row. Results: Our results indicated that COVID-19 patients’ serum levels of IL-6 significantly diminished following HP (P value≤0.001). Furthermore, a decrease in IL-6 levels following HP demonstrated the effectiveness of this approach (area under the curve [AUC]=0.7102 and P=0.0025). Conclusion: Taken together, our findings suggest HP as a promising therapeutic option in COVID-19. However, a detailed evaluation of HP’s efficacy is required in large prospective multicenter trials.