High Institute for Education and Research in Transfusion Medicine

Solid tumors remain difficult to treat due to antigen heterogeneity, physical barriers that limit immune-cell trafficking, and a profoundly immunosuppressive tumor microenvironment (TME). Over the past decade, cancer immunotherapy advanced considerably through innovative strategies, including macrophage reprogramming and CAR-macrophages, dendritic-cell (DC) vaccines, natural killer (NK) and natural killer T (NKT) cell approaches, tumor-infiltrating lymphocyte (TIL) therapy, TCR-engineered and CAR-T cells, emerging B-cell engineering, and cell-derived extracellular vesicles (EVs). Here we summarize how each modality interacts with the TME, highlight key clinical milestones (e.g., FDA approval of a TIL product for melanoma in 2024), and outline bioengineering strategies—multi-antigen targeting, cytokine armoring, trafficking cues, and safety switches—that aim to overcome resistance and toxicity. We also review EV-based, cell-free strategies that retain tumor specificity with potentially improved safety and manufacturability. Finally, we discuss remaining barriers—standardized manufacturing, on-target/off-tumor effects, limited persistence—and propose rational combinations with checkpoint blockade, radiotherapy, and targeted agents. This overview positions immune cell–based therapy as a rapidly maturing, transformative approach for solid tumors.Graphical abstract

Platelet activation is a hallmark feature of coronary artery disease (CAD), characterized by a proaggregatory and proinflammatory state. However, the proadhesive phenotype, mediated by the collagen receptors GPVI and integrin α₂β₁, seems to be critically essential in the pathogenesis of disease yet underexplored in advanced CAD patients. Given the limited insight into this area, we aimed, for the first time, to comprehensively assess the expression of adhesion receptors, as well as the collagen-dependent adhesion of platelets, in CAD patients candidates for CABG (Advanced CAD) compared to healthy controls. Twenty CAD patients scheduled for CABG surgery, selected using strict exclusion criteria, and healthy controls were analyzed for expression of GPVI, integrin α₂β₁, and P-selectin via flow cytometry. Collagen-dependent platelet adhesion and spreading under static conditions were evaluated by immunofluorescence microscopy, which was correlated with GPVI expression and platelet indices. CAD patients exhibited higher levels of GPVI and P-selectin expression, but not α2β1, along with increased platelet adhesion and spreading on a collagen matrix. Platelet functional activity was strongly linked to GPVI expression and platelet indices, including MPV and PDW. The study presented here for the first time exhibited the higher proadhesive function in advanced CAD, which significantly correlates with platelet indices. These findings indicate that a sustained proadhesive state may increase the risk of prothrombotic complications before CABG, while the indices themselves may serve as indirect surrogate markers of platelet adhesive potential. Moreover, ROC curve analysis confirmed the high sensitivity and specificity of the adhesion profile in discriminating CAD patients from healthy controls.

COVID-19 can affect hematological and biochemical parameters, potentially altering platelet function. This study aimed to evaluate the long-term effects of COVID-19 on the quality of platelet concentrates (PCs) collected from donors with a history of infection. Twenty PCs were selected from male donors who had recovered from COVID-19. Donors were divided into two groups: control (recovered more than 6 months ago) and case (recovered between 1 and 3 months ago). Research variables, including metabolic and oxidative parameters, were evaluated. Platelet aggregation was also measured at various time points during PC storage. Both groups showed significant decreases in glucose and pH, and increases in lactate, LDH activity, and ROS during storage (p < 0.001). Collagen-induced platelet aggregation declined over time in both groups without a significant difference between them (interaction p = 0.8). In contrast, arachidonate-induced aggregation showed a significant group-by-time interaction (p = 0.003), with a significant decrease over time in the case group but not in controls. Other parameters did not differ significantly between groups (p > 0.05). PC from donors recently recovered from COVID-19 exhibited a decline in aggregation in response to both collagen and arachidonic acid; however, the reduction in arachidonic acid-induced aggregation was particularly significant, indicating a selective impairment in platelet function following infection. Biochemical markers did not show significant differences between groups. Further studies with larger cohorts and clinical efficacy assessments are essential to comprehensively evaluate the safety and effectiveness of transfusing PC from donors recently recovered from COVID-19.

To prepare a therapeutic dose of platelets in adults, 4-6 platelet concentrate (PC) from whole blood or one unit of apheresis are required. This study aimed to evaluate the effect of the preparation process of apheresis-PCs and pooled-PCs from platelet-rich plasma (PRP) on the platelet microparticles (PMP) count and platelet activation during storage. This study used four apheresis-PCs from the Haemonetics MCS + and four pooled-PCs. Six PRP-PCs were pooled and filtered to prepare pooled PRP-PC. The quality of the PCs was measured by platelet count, pH, swirling, P-selectin expression (as a marker of platelet activation), and PMP count on days 1, 3, and 5. WBC and RBC count on the first day and bacterial contamination on day 5. The platelet count in the pooled PRP-PCs was significantly lower on the fifth day compared to the first day. The PMP count was significantly higher on day 5 compared to day 1 for the pooled PRP-PCs, for the apheresis-PCs, the PMP count was higher on day 3 and day 5 compared to day 1. The WBC and RBC count in the apheresis-PCs was significantly lower. The P-selectin expression on the first day in the apheresis-PCs was significantly higher. The PMP count in the apheresis-PCs was significantly higher than the pooled PRP-PCs on day 3. The pooled PRP-PCs met standard quality parameters like apheresis-PCs. Pooled PRP-PCs showed lower platelet activation and PMP compared to apheresis-PCs in the early storage, indicating potential for clinical use.

Background: Premature activation of integrin α IIb β 3 plays a central role in the induction and development of the platelet storage lesion (PSL) characterized by an exhausted platelet phenotype that affects adhesion and spreading on fibrinogen. Given the role of reactive oxygen species (ROS) in regulating platelet activation per se, we investigated the effects of a ROS scavenger on reducing the functional decline of platelet integrin α IIb β 3 during storage. Methods: Platelet-rich plasma-platelet concentrates (PRP-PCs) were either treated with ROS-reducing agents (1 mM N-acetyl-L-cysteine [NAC] or 30 μM NADPH oxidase [NOX] inhibitor, VAS2870) or kept untreated during storage. CD41/CD61 (total integrin α IIb β 3) expression and PAC-1 binding (specific to active integrin α IIb β 3 conformation) were analyzed by flow cytometry over a 5 day storage period. Molecular changes in integrin β 3 subunit were evaluated by western blotting. Platelet adhesion/spreading to fibrinogen in the presence of ROS inhibitors was also investigated during storage using fluorescence microscopy. Results: A decrease in the molecular weight of integrin β 3 subunit was observed during platelet storage, and was significantly reduced by NAC but not VAS2870, suggesting proteolytic cleavage of β 3 during storage. Further to this, ROS inhibitors decreased integrin activation and increased platelet adhesion to fibrinogen from day 3 of storage, while NAC but not VAS2870 improved platelet spreading. Conclusion: This is the first report of increasing β 3 cleavage of integrin during storage that was inversely correlated with integrin α IIb β 3-mediated platelet function. In this regard, as a generic ROS scavenger, NAC was shown to reduce defects in platelet spreading through inhibition of β 3 cleavage. This is in contrast to VAS2870 which selectively inhibits cytosolic NOX alone, suggesting that the reduced platelet function observed during storage may be due to cumulative effects of mitochondrial ROS. Taken together, these studies suggest that adding NAC to platelets may significantly preserve optimal integrin α IIb β 3 and platelet function during storage. Moreover, as a reversible scavenger, its inhibitory effect can be readily compensated after transfusion.

Acute myeloid leukemia (AML) is one of the most common blood malignancies in adults, characterized by the involvement of hematopoietic myeloid progenitors. Numerous studies have demonstrated the involvement of long noncoding RNAs (lncRNAs) in AML pathogenesis. This study aimed to investigate the expression profile of lncRNA small nuclear RNA host gene 14 (SNHG14) and its role in the pathogenesis, clinical features, and prognosis of adult non-M3 AML. The expression level of SNHG14 was evaluated in bone marrow (BM) samples obtained from 50 adult non-M3 AML patients and 49 healthy controls using Quantitative Reverse Transcription-Polymerase Chain Reaction. We also investigated the correlation between clinicopathological characteristics and SNHG14 expression levels in AML patients. The expression level of SNHG14 was significantly decreased in the BM tissues of adult non-M3 AML patients compared to healthy controls. Patients with low SNHG14 expression were associated with poor overall survival, while no correlation was found between low SNHG14 expression and relapse-free survival. Our findings suggest that SNHG14 expression could serve as a potential biomarker for prognosing adult non-M3 AML patients. Furthermore, SNHG14 may offer insights into novel therapeutic targets for this subset of AML patients.

Background: The risk assessment of research projects provides a valuable approach for designing proper methodology, assuring data reliability, and accurately forecasting the resource requirements. Although X-ray irradiation has been globally recognized as a safe method for blood bag sterilization, it has not replaced gamma irradiation in Iran. To facilitate this replacement, a suitable methodology and the assessment of the intervening factors and the risks involved are required. Therefore, this study aims to evaluate the risks associated with X-ray and gamma irradiation using Failure Mode and Effects Analysis (FMEA) as a preliminary model applied in various scientific centers. Materials and Methods: This interventional study uses FMEA to identify the failure modes in six primary processes. Severity (S), occurrence (O), and detection (D) scores were assigned to each failure mode, and their product, the Risk Priority Number (RPN), was calculated to rank the risk levels and compare the failure modes. Control and preventive measures were defined for the failure modes, and the RPN scores were re-evaluated six months later to assess their effectiveness. Results: Twenty-two failure modes with RPN scores ranging from 24 to 360 were identified and evaluated. Through defining control and preventive measures for all the analyzed failure modes, the overall risk level was reduced from a baseline RPN of 114.36 ± 94.97 to a re-scored RPN of 12.18 ± 7.64. This represents an approximately 89.45% reduction from the baseline. The reduction in RPN was primarily due to the changes in the occurrence and then detection. Conclusion: FMEA is a robust tool for analyzing and mitigating risks in research projects, enhancing their quality before implementation. By this method, the risks associated with replacing gamma irradiation with X-ray irradiation for blood bags can be identified and controlled, leading to the elimination of irradiation limitations for blood bags nationwide.