Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy. Hypoxia-inducible factors, HIF-1α and HIF-2α, are expressed in the majority of ccRCC. Targeting immune checkpoints with the blockade of PD-1 and its ligand PD-L1 reorganizes T-cell activity in tumor microenvironment and provides important antitumor responses. PD-L1 upregulation has been found to be hypoxia-inducible factor (HIF) dependent. Our aim is to demonstrate the association between PD-L1 and HIF expression and to reveal the role of PD-L1 in prognosis and its association with tumor microenvironment. Surgical specimens from 145 patients diagnosed with ccRCC, who had undergone radical or partial nephrectomy, were retrospectively analyzed. Immunohistochemistry on tissue microarrays (TMA) was performed to demonstrate expressions of PD-L1, HIF-1α, and HIF-2α in tumor cells and PD-1, CD4, and CD8 in lymphocytes to assess lymphocyte density in tumor microenvironment. PD-L1 tumor cell expression was detected in 20/125 (13.8%) cases, which correlated with higher levels of PD-1, CD4, CD8 and HIF-2α expression. Low or high expression of HIF-1α was similar in PD-L1-positive cases. When PD-L1-positive cases were compared with negative ones, there was no significant difference in terms of prognostic factors. However, the number of WHO/ISUP grade 3–4 tumors was significantly higher in PD-L1-positive cases than in negative ones. PD-L1 tumor cell expression is strongly associated with increased HIF-2α expression and presence of dense lymphocytic infiltration in ccRCCs. Our findings confirm that PD-L1 positivity is associated with high ISUP nucleolar grade. The association between PD-L1, HIF, and lymphocyte density in tumor microenvironment must be clarified and especially taken into account in combination treatment.

Immunotherapy can revolutionize anti-cancer therapy if specific targets are available. Immunogenic peptides encoded by cancer-specific genes (CSGs) may enable targeted immunotherapy, even of oligo-mutated cancers, which lack neo-antigens generated by protein-coding missense mutations. Here, we describe an algorithm and user-friendly software named RAVEN (Rich Analysis of Variable gene Expressions in Numerous tissues) that automatizes the systematic and fast identification of CSG-encoded peptides highly affine to Major Histocompatibility Complexes (MHC) starting from transcriptome data. We applied RAVEN to a dataset assembled from 2,678 simultaneously normalized gene expression microarrays comprising 50 tumor entities, with a focus on oligo-mutated pediatric cancers, and 71 normal tissue types. RAVEN performed a transcriptome-wide scan in each cancer entity for gender-specific CSGs, and identified several established CSGs, but also many novel candidates potentially suitable for targeting multiple cancer types. The specific expression of the most promising CSGs was validated in cancer cell lines and in a comprehensive tissue-microarray. Subsequently, RAVEN identified likely immunogenic CSG-encoded peptides by predicting their affinity to MHCs and excluded sequence identity to abundantly expressed proteins by interrogating the UniProt protein-database. The predicted affinity of selected peptides was validated in T2-cell peptide-binding assays in which many showed binding-kinetics like a very immunogenic influenza control peptide. Collectively, we provide an exquisitely curated catalogue of cancer-specific and highly MHC-affine peptides across 50 cancer types, and a freely available software (https://github.com/JSGerke/RAVENsoftware) to easily apply our algorithm to any gene expression dataset. We anticipate that our peptide libraries and software constitute a rich resource to advance anti-cancer immunotherapy.

What is already known on this topic? The European-Thyroid Imaging Reporting and Data System (EU-TIRADS) is a risk stratification system used to evaluate the probability of malignancy in thyroid nodules, based on ultrasound characteristics. This scoring system assists clinicians in determining whether to suggest biopsy or further monitoring of thyroid nodules. The EU-TIRADS scoring system has undergone comprehensive investigation in adult populations, demonstrating acceptable accuracy in the prediction of malignancy. The EU-TIRADS scoring system has the potential to be a useful tool for evaluating thyroid nodules in children, but its accuracy and effectiveness still require confirmation.

Background: Lung cancer remains the leading cause of cancer-related deaths worldwide, with non-small cell lung carcinomas (NSCLCs) comprising the majority of cases. Among the common driver mutations, KRAS plays a critical role in guiding treatment strategies. This study evaluates the expression of programmed death-ligand 1 (PD-L1) and hypoxia-inducible factor 1-alpha (HIF-1α) in KRAS-mutant NSCLCs and investigates their associations with clinicopathological findings. Methods: A total of 85 cases with KRAS mutations were analyzed. Immunohistochemical staining for HIF-1α and PD-L1 was performed, and their relationships with mutation status and prognostic variables were assessed. Results: A significant correlation was identified between HIF-1α expression and PD-L1 expression in tumor cells. While the KRAS G12C mutation was not significantly associated with HIF-1α expression in tumor cells, it demonstrated a notable relationship with HIF-1α expression in the tumor microenvironment and PD-L1 expression. However, PD-L1 and HIF-1α expression did not significantly influence overall survival outcomes. Conclusions: Expression of PD-L1 was positively correlated with HIF-1α, which may provide evidence for a novel therapy targeting PD-L1 and HIF-1α in NSCLC. Further comprehensive studies are warranted to elucidate the prognostic implications of tumor–microenvironment and mutation interactions.

Sevoflurane, a commonly used inhalational anesthetic, has been associated with hepatotoxicity, although reports are often isolated. Cerium oxide nanoparticles (CeO₂) are effective free radical scavengers with potential therapeutic applications for oxidative stress-related damage. This study aimed to evaluate the protective effects of CeO₂ on liver damage in sevoflurane-administered rats. A total of 24 male Wistar albino rats were randomized into four groups: Control (C), Sevoflurane (S), Cerium Oxide (CeO₂), and Sevoflurane + Cerium Oxide (S + CeO₂). Sevoflurane was administered at 2% concentration with 100% oxygen at 4 L/min for 2 h in Groups S and S + CeO₂. CeO₂ (0.5 mg/kg) was administered intravenously in Groups CeO₂ and S + CeO₂. Biochemical analyses of alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), hemoglobin (Hgb), and hematocrit (Hct) were performed, and liver tissues were examined histopathologically. Hydropic degeneration and neutrophil infiltration were significantly lower in Group CeO₂ compared to Group S. Group S showed elevated AST and LDH levels compared to the control (p < 0.05). Although AST levels were lower in Groups CeO₂ and S + CeO₂ than in Group S, the difference was not statistically significant. LDH levels were significantly lower in Group S + CeO₂ compared to Group S (p = 0.045). Histopathological examination confirmed reduced liver damage in CeO₂-treated groups. This study is of significance since it is the first experimental study on the effect of CeO2 on liver damage caused by sevoflurane. Cerium oxide demonstrated potential in mitigating sevoflurane-induced liver damage. Further research is warranted to explore the clinical relevance of CeO₂ in hepatic injury.

Objective: This study aimed to evaluate clinical characteristics, surgical management approaches, and long-term outcomes of pediatric patients with histopathologically-confirmed pancreatic solid pseudopapillary neoplasm (SPN) at a single tertiary center over 10 years. Methods: A retrospective review was conducted of 16 pediatric patients with pancreatic SPN who were treated at the hospital between 2015 and 2025. Data on demographics, clinical presentation, imaging, surgery, pathology, and follow-up were analyzed. Results: Among the 16 patients, 15 were female and 1 was male, with a median age of 14 years (range: 7-16). Abdominal pain was the most frequent presenting symptom (n=12) and other presentations included jaundice, abdominal swelling, or amenorrhea, while 2 patients reported no symptoms. The pancreatic head was the most common tumor site (n=9), and the median tumor size was 5 cm (range: 1-14 cm). Surgical procedures included enucleation (n=10), distal pancreatectomy (n=3), and the Whipple procedure (n=3). Despite positive surgical margins in 9 patients, only 2 experienced local recurrence. No patients received adjuvant therapy. Postoperative complications occurred in 2 cases. One patient developed papillary thyroid carcinoma during follow-up. The median follow-up duration was 50 months (range: 2-108), and all patients were alive and all but one are disease-free at the last evaluation. Conclusion: Pediatric pancreatic SPN predominantly affects adolescent girls and often presents incidentally. Surgical resection yields excellent long-term outcomes even in the presence of positive margins. Continued follow-up is essential due to potential recurrence and rare secondary malignancies.