mutation-related immune checkpoint molecule absent in melanoma 2 () contributes to immune infiltration in pediatric and adult acute myeloid leukemia: evidence from bioinformatics analysis.

Background: The use of FMS-like tyrosine kinase 3 () as a crucial target for kinase inhibitors is well established, but its association with immune infiltration remains unclear. This study aimed to explore the relationship between mutations and immune checkpoint molecules (ICMs) in patients with acute myeloid leukemia (AML).

Methods: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to identify the ICMs associated with mutations.

Understanding rare genetic variants within the terminal pathway of complement system in preeclampsia.

Preeclampsia is a common multifactorial disease of pregnancy. Dysregulation of complement activation is among emerging candidates responsible for disease pathogenesis. In a targeted exomic sequencing study of 609 women with preeclampsia and 2092 non-preeclamptic controls, we identified 14 variants within nine genes coding for components of the membrane attack complex (MAC, C5b-9) that are associated with preeclampsia.

Co-targeting of the thymic stromal lymphopoietin receptor to decrease immunotherapeutic resistance in CRLF2-rearranged Ph-like and Down syndrome acute lymphoblastic leukemia.

CRLF2 rearrangements occur in >50% of Ph-like and Down syndrome (DS)-associated B-acute lymphoblastic leukemia (ALL) and induce constitutive kinase signaling targetable by the JAK1/2 inhibitor ruxolitinib under current clinical investigation. While chimeric antigen receptor T cell (CART) immunotherapies have achieved remarkable remission rates in children with relapsed/refractory B-ALL, ~50% of CD19CART-treated patients relapse again, many with CD19 antigen loss. We previously reported preclinical activity of thymic stromal lymphopoietin receptor-targeted cellular immunotherapy (TSLPRCART) against CRLF2-overexpressing ALL as an alternative approach.

Leptomeningeal metastatic disease: new frontiers and future directions.

Leptomeningeal metastatic disease (LMD), encompassing entities of 'meningeal carcinomatosis', neoplastic meningitis' and 'leukaemic/lymphomatous meningitis', arises secondary to the metastatic dissemination of cancer cells from extracranial and certain intracranial malignancies into the leptomeninges and cerebrospinal fluid. The clinical burden of LMD has been increasing secondary to more sensitive diagnostics, aggressive local therapies for discrete brain metastases, and improved management of extracranial disease with targeted and immunotherapeutic agents, resulting in improved survival. However, owing to drug delivery challenges and the unique microenvironment of LMD, novel therapies against systemic disease have not yet translated into improved outcomes for these patients.

Erythrocyte-Based Biomimetic MOFs as a Triple Epigenetic Regulator for Enhancing Anti-Leukemia Immunity.

While therapeutic strategies targeting epigenetic dysregulation hold promise for leukemia, epigenetic drugs face several limitations, including low utilization rates, the emergence of resistance, and off-target effects. The hypoxic microenvironment in leukemia further impairs drug sensitivity. Here, we synthesized an MOF-based erythrocyte biomimetic nanoplatform to enhance immune responses against leukemia by targeting three epigenetic modifications.

CD7 CART Therapy Bridging Allo-HSCT Remarkably Improves Long-Term DFS in Refractory/Relapsed T-ALL/LBL.

T-ALL is caused by abnormal proliferation of T cells. It comprises 25%-50% of ALL cases in children and adults. Outlook for R/R T-ALL/LBL and patients over 60 is even dimmer.

Significant Advancements and Evolutions in Chimeric Antigen Receptor Design.

Recent times have witnessed remarkable progress in cancer immunotherapy, drastically changing the cancer treatment landscape. Among the various immunotherapeutic approaches, adoptive cell therapy (ACT), particularly chimeric antigen receptor (CAR) T cell therapy, has emerged as a promising strategy to tackle cancer. CAR-T cells are genetically engineered T cells with synthetic receptors capable of recognising and targeting tumour-specific or tumour-associated antigens.

CD47 in Osteosarcoma: Correlation with Metastasis and Macrophage-Mediated Phagocytosis.

CD47 is expressed on cell surfaces and acts as a "don't eat me" signal by interacting with signal-regulatory protein-α on the macrophage surface. Some cancer cells express CD47 protein and can evade macrophage phagocytosis. Herein, we evaluated the feasibility of targeting CD47 for osteosarcoma by analyzing its expression patterns, clinicopathological correlations, and immunotherapeutic potential.

Integration of eQTL and multi-omics comprehensive analysis of triacylglycerol synthase 1 (TGS1) as a prognostic and immunotherapeutic biomarker across pan-cancer.

An increasing number of expression quantitative trait loci (eQTLs) have been linked to tumorigenesis. In this study, we used Mendelian randomization (MR) to identify a novel cancer susceptibility gene, Trimethylguanosine Synthase 1 (TGS1). TGS1-induced hypermethylation at the 5' end of human telomerase RNA (hTR) impedes hTR accumulation, decreasing telomerase assembly factor levels and thus limiting telomere elongation, a crucial factor in tumor progression.

Immune-oncology targets and therapeutic response of cell pyroptosis-related genes with prognostic implications in neuroblastoma.

Objective: Construction of a neuroblastoma (NB) prognostic predictive model based on pyroptosis-related genes (PRGs) to improve individualized management of NB patients.

Methods: The NB cohort GSE49711 was obtained from the Gene Expression Omnibus (GEO) database, and a total of 498 patients were enrolled into the study, which were randomized into a training set and a test set at a ratio of 1:1, with 250 patients in the training set and 248 patients in the test set. A risk prediction model was constructed using the training set, and the GSE49711 cohort and test set were used as internal validation to verify the reliability of the model.

Quantifying tumor specificity using Bayesian probabilistic modeling for drug and immunotherapeutic target discovery.

In diseases such as cancer, the design of new therapeutic strategies requires extensive, costly, and unfortunately sometimes deadly testing to reveal life threatening off-target effects. We hypothesized that the disease specificity of targets can be systematically learned for all genes by jointly evaluating complementary molecular measurements of healthy tissues using a hierarchical Bayesian modeling approach. Our method, BayesTS, integrates protein and gene expression evidence and includes tunable parameters to moderate tissue essentiality.

Prognostic and Immunotherapeutic Role of TACC3 in Pancancer and Its Impact on Proliferation and Docetaxel Resistance in Lung Adenocarcinoma.

Introduction: Transforming acidic coiled-coil containing protein 3 (TACC3) exerts a vital role in cancer progression by modulating cell division and facilitating tumor growth. Given the lack of comprehensive research on the pancancer implications of TACC3, our study aimed to analyze the functional role of TACC3 in pancancer and validate it through experimental investigations in lung adenocarcinoma.

Methods: We first employed various bioinformatics techniques to investigate the expression and prognostic significance of TACC3 in pancancer.

Targeting DLK1 in neuroblastoma.

An ideal cell surface target has ubiquitously high cancer expression, absence from healthy tissues, and an essential role cancer initiation and/or maintenance. In this issue of Cancer Cell, Hamilton et al. combine proteomics, transcriptomics, epigenomics, and dependency databases to identify DLK1, a novel immunotherapeutic target for neuroblastoma.

A proteogenomic surfaceome study identifies DLK1 as an immunotherapeutic target in neuroblastoma.

Cancer immunotherapies produce remarkable results in B cell malignancies; however, optimal cell surface targets for many solid cancers remain elusive. Here, we present an integrative proteomic, transcriptomic, and epigenomic analysis of tumor and normal tissues to identify biologically relevant cell surface immunotherapeutic targets for neuroblastoma, an often-fatal childhood cancer. Proteogenomic analyses reveal sixty high-confidence candidate immunotherapeutic targets, and we prioritize delta-like canonical notch ligand 1 (DLK1) for further study.

Identification of DLK1, a Notch ligand, as an immunotherapeutic target and regulator of tumor cell plasticity and chemoresistance in adrenocortical carcinoma.

Immunotherapeutic targeting of cell surface proteins is an increasingly effective cancer therapy. However, given the limited number of current targets, the identification of new surface proteins, particularly those with biological importance, is critical. Here, we uncover delta-like non-canonical Notch ligand 1 (DLK1) as a cell surface protein with limited normal tissue expression and high expression in multiple refractory adult metastatic cancers including small cell lung cancer (SCLC) and adrenocortical carcinoma (ACC), a rare cancer with few effective therapies.

The Laws of Attraction: Chemokines as Critical Mediators in Cancer Progression and Immunotherapy Response in Bladder Cancer.

Bladder cancer (BCa) is a prevalent urogenital malignancy, characterized by a myriad of genetic and environmental risk factors that drive its progression. Approximately 75% of bladder tumors are non-muscle-invasive at diagnosis. For such cases, bladder preservation is often feasible with intravesical chemotherapy or immunotherapy.

Prognostic value of in pan-cancer analysis.

Background: Transmembrane and tetratricopeptide repeat containing 1 () is a recently discovered enzyme involved in the O-mannosylation of cadherins and protocadherins. It has been implicated in various types of cancer, but the overall prognostic significance of in pan-cancer and its potential as an immunotherapeutic target remain unclear.

Methods: We applied various bioinformatics methods to investigate the potential oncogenic roles of using public databases.

MALT1 protease inhibition restrains glioblastoma progression by reversing tumor-associated macrophage-dependent immunosuppression.

MALT1 protease is an intracellular signaling molecule that promotes tumor progression via cancer cell-intrinsic and cancer cell-extrinsic mechanisms. MALT1 has been mostly studied in lymphocytes, and little is known about its role in tumor-associated macrophages. Here, we show that MALT1 plays a key role in glioblastoma (GBM)-associated macrophages.

Developing CAR T-Cell Therapies for Pediatric Solid Tumors.

Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of hematological malignancies, inducing notable and durable clinical responses. However, for solid tumors, including but not limited to pediatric tumors, several peculiar biological features posed substantial challenges for achieving comparable results. Despite sound pre-clinical evidence of the ability of CAR T cells to eradicate solid malignancies, their activity remains suboptimal when facing the in vivo complexity of solid tumors, characterized by antigen heterogeneity, scarce T-cell infiltration, and an immunosuppressive microenvironment.

The Road Ahead in Pancreatic Cancer: Emerging Trends and Therapeutic Prospects.

This review explores the challenges and emerging trends in pancreatic cancer therapy. In particular, we focus on the tumor microenvironment and the potential of immunotherapy for pancreatic cancer. Pancreatic ductal adenocarcinoma, characterized by its dense stromal architecture, presents unique challenges for effective treatment.