Metastatic brain tumors: from development to cutting-edge treatment.

Metastatic brain tumors, also called brain metastasis (BM), represent a challenging complication of advanced tumors. Tumors that commonly metastasize to the brain include lung cancer and breast cancer. In recent years, the prognosis for BM patients has improved, and significant advancements have been made in both clinical and preclinical research.

NK cells-derived extracellular vesicles potency in the B cell lymphoma biotherapy.

Introduction: Extracellular vesicles of Natural Killer cells (NKEV) exert an antitumor effect towards hematopoietic and solid tumors and have an immune modulating effect, suggesting a promising role in immune and biotherapy. In this study, a continuation of our former works, we demonstrated a network by mass spectrometry analysis between NKEV protein cargo and antitumor effects. Human healthy NKEV, both exosomes and microvesicles, have a significant and direct cytotoxic effect against human B cell lymphoma in and conditions.

Dura immunity configures leptomeningeal metastasis immunosuppression for cerebrospinal fluid barrier invasion.

The cerebrospinal fluid (CSF) border accommodates diverse immune cells that permit peripheral cell immunosurveillance. However, the intricate interactions between CSF immune cells and infiltrating cancer cells remain poorly understood. Here we use fate mapping, longitudinal time-lapse imaging and multiomics technologies to investigate the precise origin, cellular crosstalk and molecular landscape of macrophages that contribute to leptomeningeal metastasis (LM) progression.

Perioperative immunotherapy plus chemotherapy versus chemotherapy alone for patients with resectable pulmonary lymphoepithelioma-like carcinoma.

Background: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare subtype of non-small-cell lung cancer. This study aims to compare the efficacy and safety of perioperative PD-1/PD-L1 inhibitor plus chemotherapy versus chemotherapy alone in stage II-IIIB PLELC patients.

Patients And Methods: This retrospective study included stage II-IIIB PLELC patients.

STK11 mutations correlate with poor prognosis for advanced NSCLC treated with first-line immunotherapy or chemo-immunotherapy according to KRAS, TP53, KEAP1, and SMARCA4 status.

Background: The upfront treatment of non-oncogene-addicted NSCLC relies on immunotherapy alone (ICI) or in combination with chemotherapy (CT-ICI). Genomic aberrations such as KRAS, TP53, KEAP1, SMARCA4, or STK11 may impact survival outcomes.

Methods: We performed an observational study of 145 patients treated with first-line IO or CT-ICI for advanced non-squamous (nsq) NSCLC at our institution tested with an extensive lab-developed NGS panel.

Ecteinascidin synthetic analogues: a new class of selective inhibitors of transcription, exerting immunogenic cell death in refractory malignant pleural mesothelioma.

Background: Malignant pleural mesothelioma (MPM) is a highly chemo-refractory and immune-evasive tumor that presents a median overall survival of 12-14 months when treated with chemotherapy and immunotherapy. New anti-tumor therapies as well as the concomitant reactivation of immune destruction are urgently needed to treat patients with this tumor. The aim of this work is to investigate the potential effect of ecteinascidin derivatives as lurbinectedin as new first-line treatment option in MPM, alone and in combination with immunotherapy.

Single-cell RNA seq-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma.

Background & Aims: The combination of atezolizumab and bevacizumab (atezo+bev) is the current standard of care for advanced hepatocellular carcinoma (HCC), providing a median overall survival (OS) of 19.2 months. Here, we aim to uncover the underlying cellular processes driving clinical benefit versus resistance to atezo+bev.

Effects of different-valent vaccines against human papillomavirus (HPV) to prevent persistent HPV16/18 infections and CIN2+ in women: a systematic review and network meta-analysis.

Objectives: To evaluate the efficacy of 2-valent, 4-valent and 9-valent HPV vaccination in preventing persistent HPV infections and cervical intraepithelial neoplasia grade 2 or higher (CIN2+) lesions among women with different infection statuses at baseline.

Methods: PubMed, Web of Science, Cochrane, Embase and ClinicalTrials.gov were searched from their inception to March 2024.

Artificial neural network systems to predict the response to sintilimab in squamous-cell non-small-cell lung cancer based on data of ORIENT-3 study.

Background: Existing biomarkers and models for predicting response to programmed cell death protein 1 monoclonal antibody in advanced squamous-cell non-small cell lung cancer (sqNSCLC) did not have enough accuracy. We used data from the ORIENT-3 study to construct artificial neural network (ANN) systems to predict the response to sintilimab for sqNSCLC.

Methods: Four ANN systems based on bulk RNA data to predict disease control (DC), immune DC (iDC), objective response (OR) and immune OR (iOR) were constructed and tested for patients with sqNSCLC treated with sintilimab.

Is Whole-Brain Radiotherapy for Brain Metastases an Overestimated Therapy? A Retrospective Study of Real-World Data Using Landmark Analyses.

Background: The role of whole-brain radiotherapy for patients with brain metastases is changing as immunotherapy and molecularly targeted therapies advance. However, whole-brain radiotherapy continues to be part of the multimodal concept.

Methods: This retrospective study included 285 patients who received whole-brain radiotherapy for brain metastases, using a median dose of 30 Gy.

Potassium/sodium cation carriers robustly up-regulate CD20 antigen by targeting MYC, and synergize with anti-CD20 immunotherapies to eliminate malignant B cells.

Our investigation uncovers that nanomolar concentrations of salinomycin, monensin, nigericin, and narasin (a group of potassium/sodium cation carriers) robustly enhance surface expression of CD20 antigen in B-cell-derived tumor cells, including primary malignant cells of chronic lymphocytic leukemia and diffuse large B-cell lymphoma. Experiments in vitro, ex vivo, and animal model reveal a novel approach of combining salinomycin or monensin with therapeutic anti-CD20 monoclonal antibodies or anti-CD20 CAR-T cells, significantly improving non- Hodgkin lymphoma (NHL) therapy. The results of RNA-seq, genetic editing, and chemical inhibition delineate the molecular mechanism of CD20 upregulation, at least partially, to the downregulation of MYC, the transcriptional repressor of the MS4A1 gene encoding CD20.

Clinical perspectives on the value of testing for and mutations in advanced NSCLC.

Standard first-line therapy for patients with metastatic non-small cell lung cancer (mNSCLC) without identified actionable mutations consists of regimens comprising immune checkpoint inhibitors (ICIs), alone or in combination with platinum-based chemotherapy (CTx). However, approximately 20-30% of patients with mNSCLC (including some patients with high tumor programmed cell death ligand-1 expression) display primary resistance to ICIs, either alone or in combination with CTx. Mutations in tumor suppressor genes (), and () often detected in patients with mutations, are associated with an aggressive disease phenotype and resistance to standard ICI regimens.

Predicting the tumor microenvironment composition and immunotherapy response in non-small cell lung cancer from digital histopathology images.

Immune checkpoint inhibitors (ICI) have become integral to treatment of non-small cell lung cancer (NSCLC). However, reliable biomarkers predictive of immunotherapy efficacy are limited. Here, we introduce HistoTME, a novel weakly supervised deep learning approach to infer the tumor microenvironment (TME) composition directly from histopathology images of NSCLC patients.

Disrupting Notch signaling related HES1 in myeloid cells reinvigorates antitumor T cell responses.

Background: Tumor-associated macrophages (TAMs) are immunosuppressive cells within the tumor microenvironment (TME) that hinder anti-tumor immunity. Notch signaling is a pathway crucial for TAM differentiation and function. Here, we investigate the role of HES1, a downstream target of Notch signaling, in TAM-mediated immunosuppression and explore its potential as a target for cancer immunotherapy.

Zinc-based radioenhancers to activate tumor radioimmunotherapy by PD-L1 and cGAS-STING pathway.

Radiotherapy and immunotherapy have already become the primary form of treatment for non-small-cell lung cancer (NSCLC), but are limited by high radiotherapy dose and low immune response rate. Herein, a multi-pronged strategy using a radio-immuno-enhancer (ZnO-Au@mSiO) is developed by inducing tumor cells apoptosis and reprograming the immunosuppressive tumor microenvironment (TME). The radio-immuno-enhancer employed Au as a radiosensitizer, transition Zn ions as immune activators, which not only tremendously enhances the anti-proliferative activity of radiotherapy toward cancer cells, but also activates the immune response with multi-targets to let "exhausted" T cells "back to life" by triggering immunogenic cell death (ICD), immune checkpoint blockade (ICB) that target PD-1/PD-L1 and cGAS-STING under X-ray irradiation with a low dosage.

The landscape of primary mismatch repair deficient gliomas in children, adolescents, and young adults: a multi-cohort study.

Background: Gliomas are a major cause of cancer-related death among children, adolescents, and young adults (age 0-40 years). Primary mismatch repair deficiency (MMRD) is a pan-cancer mechanism with unique biology and therapeutic opportunities. We aimed to determine the extent and impact of primary MMRD in gliomas among children, adolescents, and young adults.

Integrative multi-omics and machine learning approach reveals tumor microenvironment-associated prognostic biomarkers in ovarian cancer.

Background: Ovarian cancer (OC) is a globally prevalent malignancy with significant morbidity and mortality, yet its heterogeneity poses challenges in treatment and prognosis. Recognizing the crucial role of the tumor microenvironment (TME) in OC progression, this study leverages integrative multi-omics and machine learning to uncover TME-associated prognostic biomarkers, paving the way for more personalized therapeutic interventions.

Methods: Employing a rigorous multi-omics approach, this study analyzed single-cell RNA sequencing (scRNA-seq) data from OC and normal tissue samples, including high-grade serous OC (HGSOC) from the Gene Expression Omnibus (GEO: GSE184880) and The Cancer Genome Atlas (TCGA) OC cohort, utilizing the Seurat package to annotate 700 TME-related genes.

Management of translocation carcinomas of the kidney.

Microphthalmia-associated transcription factor family translocation renal cell carcinoma (MiT-tRCC) stands out as a rare subtype of kidney cancer with distinct biological features compared to other kidney cancer subtypes. It encompasses TFE3-rearranged RCC (also known as Xp11 translocation RCC) and TFE-rearranged translocations RCC, although multiple new fusion partners were identified. Traditionally thought to primarily affect children and young adults, more cases of MiT-tRCC are being identified in adults.

Pemigatinib combined with immunotherapy and stereotactic body radiation therapy for FGFR2 fusion-positive advanced intrahepatic cholangiocarcinoma with brain metastasis: a Case Report.

Background: FGFR2 fusions or rearrangements occur in 13%-20% of patients with intrahepatic cholangiocarcinoma (iCCA). Pemigatinib, a representative FGFR inhibitor, is commonly used for targeted therapy in such patients. Additionally, brain metastasis (BM) is extremely rare in advanced iCCA, and there is currently no standard treatment strategy for advanced iCCA patients with BM.

Pushing the boundaries of radiotherapy-immunotherapy combinations: highlights from the 7 immunorad conference.

Over the last decade, the annual Immunorad Conference, held under the joint auspicies of Gustave Roussy (Villejuif, France) and the Weill Cornell Medical College (New-York, USA) has aimed at exploring the latest advancements in the fields of tumor immunology and radiotherapy-immunotherapy combinations for the treatment of cancer. Gathering medical oncologists, radiation oncologists, physicians and researchers with esteemed expertise in these fields, the Immunorad Conference bridges the gap between preclinical outcomes and clinical opportunities. Thus, it paves a promising way toward optimizing radiotherapy-immunotherapy combinations and, from a broader perspective, improving therapeutic strategies for patients with cancer.

Transcriptome-aligned metabolic profiling by SERSome reflects biological changes following mesenchymal stem cells expansion.

Background: Mesenchymal stem cells (MSCs) are widely applied in the treatment of various clinical diseases and in the field of medical aesthetics. However, MSCs exhibit greater heterogeneity limited stability, and more complex molecular and mechanistic characteristics compared to conventional drugs, making rapid and precise monitoring more challenging.

Methods: Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive, tractable and low-cost fingerprinting technique capable of identifying a wide range of molecules related to biological processes.