Genetic ancestry superpopulations show distinct prevalence and outcomes across pediatric central nervous system tumors from the PBTA and PNOC.

Background: Central nervous system (CNS) tumors lead to cancer-related mortality in children. Genetic ancestry-associated cancer prevalence and outcomes have been studied, but is limited.

Methods: We performed genetic ancestry prediction in 1,452 pediatric patients with paired normal and tumor whole genome sequencing from the Open Pediatric Cancer (OpenPedCan) project to evaluate the influence of reported race and ethnicity and ancestry-based genetic superpopulations on tumor histology, molecular subtype, survival, and treatment.

Complement C3 of tumor-derived extracellular vesicles promotes metastasis of RCC via recruitment of immunosuppressive myeloid cells.

Heterogeneous roles of complement C3 have been implicated in tumor metastasis and are highly context dependent. However, the underlying mechanisms linking C3 to tumor metastasis remain elusive in renal cell carcinoma (RCC). Here, we demonstrate that C3 of RCC cell-derived extracellular vesicles (EVs) contributes to metastasis via polarizing tumor-associated macrophages (TAMs) into the immunosuppressive phenotype and recruiting polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs).

PARP12-mediated ADP-ribosylation contributes to breast cancer cell fate by regulating AKT activation and DNA-damage response.

Breast cancer represents the primary cause of death of women under 65 in developed countries, due to the acquisition of multiple drug resistance mechanisms. The PI3K/AKT pathway is one of the major regulating mechanisms altered during the development of endocrine resistance and inhibition of steps in this signalling pathway are adopted as a key strategy to overcome this issue. ADP-ribosylation is a post-translational modification catalysed by PARP enzymes that regulates essential cellular processes, often altered in diseases.

Characterization of different clinical presentation of Merkel cell carcinomas and their potential prognostic implications.

Background: Recent studies analyzed the impact of Merkel cell polyomavirus (MCPyV) on the prognosis of Merkel cell carcinoma (MCC) patients. No data on specific morphological clinical differences of MCPyV+ or MCPyV- are currently available neither on the possible prognostic implication of different clinical presentation of MCC.

Objectives: 1) to describe clinicopathological characteristics of MCC patients and the prevalence of MCPyV infection in an Italian cohort of patients; 2) to define possible differences in clinicopathological and prognostic features among MCPyV+ and MCPyV- MCCs.

Development, Validation, and Application of the Paya Hamsan Technologies Underivatized Newborn Screening Assay (PHUNSA) for Inborn Metabolic Disorders in Dried Blood Spot Samples from Iranian Infants.

Screening for inborn metabolic disorders (IMDs) in newborns is an important way to prevent serious metabolic and developmental difficulties that can result in lasting disabilities or even death. Electrospray ionization tandem mass spectrometry (MS/MS) provides an efficacious newborn blood spot screening (NBS) mechanism for analyzing dried blood spot specimens (DBSs) for biochemical markers for these conditions. Where possible, the elimination of derivatization in specimen preparation can simplify and streamline analysis.

Identification and validation of a T cell receptor targeting KRAS G12V in HLA-A*11:01 pancreatic cancer patients.

T cells targeting a KRAS mutation can induce durable tumor regression in some patients with metastatic epithelial cancer. It is unknown whether T cells targeting mutant KRAS that are capable of killing tumor cells can be identified from peripheral blood of patients with pancreatic cancer. We developed an in vitro stimulation approach and identified HLA-A*11:01-restricted KRAS G12V-reactive CD8+ T cells and HLA-DRB1*15:01-restricted KRAS G12V-reactive CD4+ T cells from peripheral blood of 2 out of 6 HLA-A*11:01-positive patients with pancreatic cancer whose tumors expressed KRAS G12V.

Vascular HIF2 Signaling Prevents Cardiomegaly, Alveolar Congestion, and Capillary Remodeling During Chronic Hypoxia.

Background: Hypoxia is associated with the onset of cardiovascular diseases including cardiac hypertrophy and pulmonary hypertension. HIF2 (hypoxia-inducible factor 2) signaling in the endothelium mediates pulmonary arterial remodeling and subsequent elevation of the right ventricular systolic pressure during chronic hypoxia. Thus, novel therapeutic opportunities for pulmonary hypertension based on specific HIF2 inhibitors have been proposed.

MicroRNA Expression in High-Grade B-Cell Lymphoma With 11q Aberration.

Mature aggressive B-cell lymphomas, such as Burkitt lymphoma (BL) and Diffuse large B-cell lymphoma (DLBCL), show variations in microRNA (miRNA) expression. The entity of High-grade B-cell lymphoma with 11q aberration (HGBCL-11q) shares several biological features with both BL and DLBCL but data on its miRNA expression profile are yet scarce. Hence, this study aims to analyze the potential differences in miRNA expression of HGBCL-11q compared to BL and DLBCL.

Identification of an immunological signature of long COVID syndrome.

Introduction: Acute COVID-19 infection causes significant alterations in the innate and adaptive immune systems. While most individuals recover naturally, some develop long COVID (LC) syndrome, marked by persistent or new symptoms weeks to months after SARS-CoV-2 infection. Despite its prevalence, there are no clinical tests to distinguish LC patients from those fully recovered.

Col1A1 as a new decoder of clinical features and immune microenvironment in ovarian cancer.

Backgrounds: Collagen type I alpha 1 chain (COL1A1) is a key protein encoding fibrillar collagen, playing a crucial role in the tumor microenvironment (TME) due to its complex functions and close association with tumor invasiveness. This has made COL1A1 a focal point in cancer biology research. However, studies investigating the relationship between COL1A1 expression levels and clinical characteristics of ovarian cancer (OC) remain limited.

Golgi protein 73: the driver of inflammation in the immune and tumor microenvironment.

Golgi Protein 73 (GP73) is a Golgi-resident protein that is highly expressed in primary tumor tissues. Initially identified as an oncoprotein, GP73 has been shown to promote tumor development, particularly by mediating the transport of proteins related to epithelial-mesenchymal transition (EMT), thus facilitating tumor cell EMT. Though our previous review has summarized the functional roles of GP73 in intracellular signal transduction and its various mechanisms in promoting EMT, recent studies have revealed that GP73 plays a crucial role in regulating the tumor and immune microenvironment.

Infiltrating T lymphocytes and tumor microenvironment within cholangiocarcinoma: immune heterogeneity, intercellular communication, immune checkpoints.

Cholangiocarcinoma is the second most common primary liver cancer, and its global incidence has increased in recent years. Radical surgical resection and systemic chemotherapy have traditionally been the standard treatment options. However, the complexity of cholangiocarcinoma subtypes often presents a challenge for early diagnosis.

Alternative splicing of modulatory immune receptors in T lymphocytes: a newly identified and targetable mechanism for anticancer immunotherapy.

Alternative splicing (AS) is a mechanism that generates translational diversity within a genome. Equally important is the dynamic adaptability of the splicing machinery, which can give preference to one isoform over others encoded by a single gene. These isoform preferences change in response to the cell's state and function.

Prognostic value of immunosuppression scores in patients with esophageal squamous cell carcinoma: a multicenter study.

Introduction: The prognostic impact of human leukocyte antigen-E (HLA-E) expression and the proportion of natural killer (NK) cells in esophageal squamous cell carcinoma (ESCC) was investigated.

Methods: This study retrospectively evaluated 397 ESCC patients across two centers. The cumulative incidence of recurrence (CIR) and the incidence of tumor-related death (CID) were analyzed in various groups.

Hepatoid adenocarcinoma of the stomach with ideal response to neoadjuvant chemo-immunotherapy: a case report.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer characterized by histological features resembling hepatocellular carcinoma. Surgical intervention remains the preferred treatment modality for eligible patients. However, the efficacy of neoadjuvant therapy and alternative treatment regimens has been found to be suboptimal.

Impact of glioma metabolism-related gene ALPK1 on tumor immune heterogeneity and the regulation of the TGF-β pathway.

Background: Recent years have seen persistently poor prognoses for glioma patients. Therefore, exploring the molecular subtyping of gliomas, identifying novel prognostic biomarkers, and understanding the characteristics of their immune microenvironments are crucial for improving treatment strategies and patient outcomes.

Methods: We integrated glioma datasets from multiple sources, employing Non-negative Matrix Factorization (NMF) to cluster samples and filter for differentially expressed metabolic genes.

Unfolded protein responses in T cell immunity.

Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are integral to T cell biology, influencing immune responses and associated diseases. This review explores the interplay between the UPR and T cell immunity, highlighting the role of these cellular processes in T cell activation, differentiation, and function. The UPR, mediated by IRE1, PERK, and ATF6, is crucial for maintaining ER homeostasis and supporting T cell survival under stress.

Extracellular matrix re-normalization to improve cold tumor penetration by oncolytic viruses.

Immunologically inert or cold tumors pose a substantial challenge to the effectiveness of immunotherapy. The use of oncolytic viruses (OVs) to induce immunogenic cell death (ICD) in tumor cells is a well-established strategy for initiating the cancer immunity cycle (CIC). This process promotes the trafficking and infiltration of CD8+ T cells into tumors, thereby eliciting a tumor-specific immune response.

Comprehensive analysis of the prognostic, immunological, and diagnostic roles of SIRT1 in pan-cancer and its validation in KIRC.

Background: Disturbances in DNA damage repair may lead to cancer. SIRT1, an NAD+-dependent deacetylase, plays a crucial role in maintaining cellular homeostasis through the regulation of processes such as histone posttranslational modifications, DNA repair, and cellular metabolism. However, a comprehensive exploration of SIRT1's involvement in pan-cancer remains lacking.

Dual T cell depleted haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide and anti-thymocyte globulin as a third salvage transplant for leukocyte adhesion deficiency with graft failure: a case report.

Background: With recent advances in clinical practice, including the use of reduced-toxicity conditioning regimens and innovative approaches such as ex vivo TCRαβ/CD19 depletion of haploidentical donor stem cells or post-transplant cyclophosphamide (PTCY), hematopoietic stem cell transplantation (HSCT) has emerged as a curative treatment option for a growing population of patients with inborn errors of immunity (IEI). However, despite these promising developments, graft failure (GF) remains a significant concern associated with HSCT in these patients. Although a second HSCT is the only established salvage therapy for patients who experience GF, there are no uniform, standardized strategies for performing these second transplants.

Bibliometric analysis of metformin as an immunomodulator (2013-2024).

Background: Metformin, the frontline treatment for diabetes, has considerable potential as an immunomodulator; however, detailed bibliometric analyses on this subject are limited.

Methods: This study extracted 640 relevant articles from the Web of Science (WOS) Core Collection and conducted visual analyses using Microsoft Excel, VOSviewer, and CiteSpace.

Results: The findings showed that research on the immunomodulatory function of metformin has grown steadily since 2017, with China and the United States being the leading contributors.

Pseudoprogression in CAR-T cell therapy for solid tumor: Case report.

We reported the pseudoprogression in an elderly patient with advanced gastric cancer after chimeric antigen receptor (CAR)-T cell therapy. The hepatic metastases enlarged 1 month after CAR-T cell infusion and then shrunk the next month as seen through computed tomography scanning. Based on a comprehensive evaluation that includes imaging, pathology, serum tumor markers, and clinical symptoms, we arrived at a diagnosis of pseudoprogression after CAR-T cell therapy, which has not been reported in previous studies.

Expression of miR-15b-5p and toll-like receptor4 as potential novel diagnostic biomarkers for hepatitis C virus-induced hepatocellular carcinoma.

Objectives: Globally, hepatocellular Carcinoma (HCC) ranks seventh in women's cancer and fifth in men's cancer. Early identification can minimize mortality and morbidity. MicroRNAs and Toll-like receptors have been suggested as potential new biomarkers for HCC; Therefore, we explored Toll-like receptor 4 (TLR-4) and miRNA 15b-5p as new non-invasive HCC biomarkers and early detection approaches.

Advancements and Future Directions of Dual-Target Chimeric Antigen Receptor T-Cell Therapy in Preclinical and Clinical Studies.

In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has made groundbreaking progress in the treatment of various cancer types, particularly hematological malignancies. In the meantime, various preclinical and clinical studies have extensively explored dual-target CAR-T therapies which can be designed to recognize two antigens simultaneously based on the immunophenotype of tumor cells. Compared with single-target CAR-T approach, dual-target CAR-T therapies demonstrate varying degrees of superior antitumor CAR effects, prevent antigen escape and relapse, reduce on-target off-tumor effects, and ensure durable responses in different types of cancer.

Access to CARe: A Narrative of Real-World Medical Decision-Making to Access Chimeric Antigen Receptor (CAR) T-Cell Therapy in Children, Adolescents, and Young Adults.

Chimeric antigen receptor (CAR) T-cell therapy is a potentially life-saving treatment for children with relapsed/refractory B-cell hematologic malignancies, and remains an important investigational therapy for other childhood cancers. Yet, access to this class of therapies remains suboptimal through both commercial use and clinical trials, especially in children, adolescents, and young adults. Using a series of case-based discussions, we outline guidance on real-world medical decision-making, and offer potential solutions to enhancing access to CAR T-cell therapy as a treatment modality.