Pretreatment with IL-15 and IL-18 rescues natural killer cells from granzyme B-mediated apoptosis after cryopreservation.

Human natural killer (NK) cell-based therapies are under assessment for treating various cancers, but cryopreservation reduces both the recovery and function of NK cells, thereby limiting their therapeutic feasibility. Using cryopreservation protocols optimized for T cells, here we find that ~75% of NK cells die within 24 h post-thaw, with the remaining cells displaying reduced cytotoxicity. Using CRISPR-Cas9 gene editing and confocal microscopy, we find that cryopreserved NK cells largely die via apoptosis initiated by leakage of granzyme B from cytotoxic vesicles.

Long-term cardiotoxicity in germ cell cancer survivors after platinum-based chemotherapy: cardiac MR shows impaired systolic function and tissue alterations.

Objectives: Long-term toxicities of germ cell cancer (GCC) treatment are of particular importance in young men with a life expectancy of several decades after curative treatment. This study aimed to investigate the long-term effects of platinum-based chemotherapy on cardiac function and myocardial tissue in GCC survivors by cardiac magnetic resonance (CMR) imaging.

Methods: Asymptomatic GCC survivors ≥ 3 years after platinum-based chemotherapy and age-matched healthy controls underwent CMR assessment, including left ventricular (LV) and right ventricular (RV) ejection fraction (EF), strain analysis, late gadolinium enhancement (LGE) imaging, and T1/T2 mapping.

Epitope base editing CD45 in hematopoietic cells enables universal blood cancer immune therapy.

In the absence of cell surface cancer-specific antigens, immunotherapies such as chimeric antigen receptor (CAR) T cells, monoclonal antibodies, or bispecific T cell engagers typically target lineage antigens. Currently, such immunotherapies are individually designed and tested for each disease. This approach is inefficient and limited to a few lineage antigens for which the on-target/off-tumor toxicities are clinically tolerated.

Next-Generation CAR T-cell Therapies.

CD19- and B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cells have enabled unprecedented responses in a subset of refractory patients with B-cell and plasma cell malignancies, leading to their approval by the FDA for the treatment of leukemia, lymphoma, and myeloma. These "living drugs" can become part of a synthetic immune system, persisting at least a decade in some patients. However, despite this tremendous impact, significant unmet treatment needs remain for patients with hematologic malignancies and solid cancers.

Approaches of stem cell mobilization in a large cohort of metastatic germ cell cancer patients.

High-dose chemotherapy (HD-Cx) in refractory germ cell cancer (GCC) is effective but limited data are available concerning the optimal approach for stem cell mobilization (SCM) in these patients. In this analysis 102 patients undergoing SCM during first (n = 25) or subsequent treatment lines (n = 77) were analyzed. Subcutaneous injections of granulocyte colony-stimulating factor (G-CSF) were given once daily (group 1) in 52 patients (51%), twice daily (group 2) in 39 patients (38%) or one injection Pegylated-G-CSF (PegG-CSF) (group 3) in eleven patients (11%) after one cycle of mobilization chemotherapy.

Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma.

Introduction: Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy.

Methods: We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe.

Newly diagnosed isolated myeloid sarcoma-paired NGS panel analysis of extramedullary tumor and bone marrow.

Isolated myeloid sarcoma (MS) is a rare malignancy in which myeloid blast forms tumors at various locations while the bone marrow (BM) remains cytomorphologically free from disease. We analyzed isolated MS from four patients and their BMs at initial diagnosis and follow-up, using a custom next-generation sequencing (NGS) panel. We observed possible clonal evolution and a clonal hematopoiesis of indeterminate potential (CHIP)-like finding in the BM of one of three cases with detectable mutations.

Successful Treatment of Delayed Methotrexate Clearance Using Glucarpidase Dosed on Ideal Body Weight in Obese Patients.

Delayed methotrexate (MTX) elimination after treatment with high-dose (HD) MTX may result in life-threatening toxicities as well as acute kidney injury (AKI). Treatment includes administration of glucarpidase, an enzyme that rapidly inactivates MTX. Dosing of glucarpidase is based on body weight; however, recommendations for dosage adjustments in obese patients are lacking.

Fatal Myelotoxicity Following Palliative Chemotherapy With Cisplatin and Gemcitabine in a Patient With Stage IV Cholangiocarcinoma Linked to Post Mortem Diagnosis of Fanconi Anemia.

Unrecognized genome instability syndromes can potentially impede the rational treatment of cancer in rare patients. Identification of cancer patients with a hereditary condition is a compelling necessity for oncologists, giving varying hypersensitivities to various chemotherapeutic agents or radiation, depending on the underlying genetic cause. Omission of genetic testing in the setting of an overlooked hereditary syndrome may lead to unexpected and unbearable toxicity from oncological standard approaches.

Correction to: DNA methylation-based reclassification of olfactory neuroblastoma.

In the original publication, the second name of the twentieth author was incorrect. It should read as 'Miguel Sáinz-Jaspeado'. The original publication of the article has been updated to reflect the change.

DNA methylation-based reclassification of olfactory neuroblastoma.

Olfactory neuroblastoma/esthesioneuroblastoma (ONB) is an uncommon neuroectodermal neoplasm thought to arise from the olfactory epithelium. Little is known about its molecular pathogenesis. For this study, a retrospective cohort of n = 66 tumor samples with the institutional diagnosis of ONB was analyzed by immunohistochemistry, genome-wide DNA methylation profiling, copy number analysis, and in a subset, next-generation panel sequencing of 560 tumor-associated genes.

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting.

Canonical Wnt Signaling Drives Tumor-Like Lesions from Sox2-Positive Precursors of the Murine Olfactory Epithelium.

Canonical Wnt signaling is known to promote proliferation of olfactory stem cells. In order to investigate the effects of a constitutive activation of Wnt signaling in Sox2-positive precursor cells of the olfactory epithelium, we used transgenic mice that allowed an inducible deletion of exon 3 of the Ctnnb1 gene, which is responsible for the phosphorylation and degradation of Ctnnb1 protein. After induction of aberrant Wnt activation by Ctnnb1 deletion at embryonic day 14, such mice developed tumor-like lesions in upper parts of the nasal cavity.