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.

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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.

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<0.0001). Also, the average CK-MB level in dead patients was 60.84 U/L, while in recovered patients was 35.17 U/L (P=00.0026). Conclusion: Elevated levels of LDH and CK-MB following COVID-19 disease increase the risk of death in these patients.