Gene editing
Cancer remains a leading global health challenge, necessitating continuous advancements in diagnostics and therapeutics to enhance patient outcomes. According to the recent data of the American Cancer Society, an estimated 20 million new cancer cases and 9.7 million cancer deaths occurred globally i…
The innovative clustered regularly interspaced short palindromic repeats (CRISPR) associated nuclease 9 (Cas9) gene editing technique may represent a suitable therapeutic opportunity for the treatment of inherited diseases such as Wilson disease (WD). This monogenetic liver disease is based on a mut…
Genomics
Steroid-refractory (SR) disease develops in a substantial fraction of patients with grade II-IV acute graft-versus-host disease (aGvHD) and is associated with poor long-term survival. Improved mechanistic insight is needed to identify reliable predictors of steroid resistance. We retrospectively pro…
UK Biobank is the world’s most comprehensive longitudinal population-based data and biosample resource. Twenty years after UK Biobank was first established, the incidence of dementia among participants is rising and is set to increase rapidly over the next 5-10 years, creating a distinct opportunity…
Immunotherapy
Bladder cancer is one of the most common malignancies of the urinary tract. Among its subtypes, muscle invasive bladder cancer (MIBC) is particularly aggressive and often associated with poor prognosis. The efficacy of platinum-based neoadjuvant chemotherapy and radical cystectomy remains unsatisfac…
Immune activation within tumors is governed by highly dynamic redox and mitochondrial signaling events, yet the temporal organization of these processes remains poorly defined. Here, we report a programmable DNAzyme nanocatalyst (APTZ) that enables time-dependent redox-immune coupling by translating…
Colorectal cancer (CRC) remains a leading cause of cancer mortality worldwide, with clinical progress limited by intratumoural cellular diversity and the absence of robust, informative markers….
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, yet their efficacy in colorectal cancer (CRC) remains limited to a minority of patients with microsatellite instability-high (MSI-H) tumors, leaving the majority with microsatellite stable (MSS) disease unresponsive. The gut m…
Immunotherapy Response in Microsatellite Instability-High Gastroesophageal Adenocarcinoma.
2026-04-15
Comprehensive clinical data stratified by microsatellite instability (MSI) status in gastroesophageal adenocarcinoma (GEA) are limited….
Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy associated with high recurrence rates and substantial treatment-related morbidity. Radiation therapy remains a central component of the management of locoregional disease. Although radiation directly damages malignant cells th…
Hepatocellular carcinoma (HCC) often exhibits limited responsiveness to immune checkpoint inhibitors (ICIs), largely due to an immunosuppressive tumor microenvironment (TME). Regulated cell death (RCD) pathways, including ferroptosis, necroptosis, and pyroptosis, possess immunogenic properties that …
Pediatric solid tumors remain among the most treatment-refractory childhood malignancies, defined by biological features that have largely resisted the immunotherapeutic advances transforming adult oncology. Exceptionally low tumor mutational burden, sparse neoantigen landscapes, and profoundly immu…
B cells have become one of the important participants in anti-tumor immunity. Compared with DCs and macrophages, B cells have unique advantages in presenting low-abundance antigens to T cells. Fatty acids play a key role in the metabolic adaptation of B cells. Whether the APC function of B cells can…
Immunotherapy “stop and go” and early discontinuation: A viable option in limited resources setting.
2026-04-15
BackgroundImmunotherapy (IO) has transformed cancer treatment, improving survival across various malignancies. However, optimal treatment duration and dosing regimens remain unclear. In low- and middle-income countries like Tunisia, access to IO is hindered by financial and logistical constraints, o…
Macrophages exhibit extensive tumor infiltration capacity across diverse solid malignancies, establishing macrophage-targeted immunotherapies as an emerging frontier in oncology. Genetic engineering of macrophages using chimeric antigen receptor (CAR) technology – enabling recognition and phagocytos…
Primary and metastatic brain tumors exhibit resistance to immunotherapies that demonstrate efficacy in peripheral cancer settings. While many immunotherapies aim to enhance CD8+ T cell infiltration and functionality in established tumors, identification of neoantigens support emerging immunopreventa…
The therapeutic efficacy of immune checkpoint inhibitors in hepatocellular carcinoma (HCC) remains limited, with programmed death receptor-1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) blockade effective in only some patients. Here, we report that phenethyl isothiocyanate (PEITC), a bioactive ph…
NK cells hold great promise for cancer immunotherapy owing to their intrinsic capacity to recognize and eliminate malignant cells. Nevertheless, broad clinical deployment is hindered by NK-cell properties like poor expansion and refractoriness to genetic modification, as well as by tumor immune-evas…
Update on pleural mesothelioma.
2026-04-15
Pleural mesothelioma remains a universally lethal cancer with a rising global burden. This underscores the need for pulmonologists to stay abreast of evolving diagnostic and therapeutic strategies….
GPNMB Drives Brain Metastasis by Sculpting a Pathological Endothelial-Immune Interactome.
2026-04-15
Brain metastases (BM) remain a devastating disease with dismal prognosis. How circulating tumor cells (CTCs) penetrate the blood brain barrier (BBB) and reprogram the brain microenvironment remain unclear. Using spatially resolved multi-omic profiling of CTCs and brain metastases, integrated with ex…
Predicting response to immune checkpoint inhibitor plus tyrosine kinase inhibitor (IO + TKI) therapy in metastatic renal cell carcinoma (mRCC) remains challenging. Forkhead box protein O1 (FOXO1) is a key transcription factor regulating tumor suppression and T cell immunity, but its clinic…
The use of mRNA therapies has innovated the clinical progress of cancer immunotherapy. However, current immunotherapeutic approaches are unable to achieve site- or immune-cell-specific delivery, resulting in adverse immune responses in off-target tissues. In addition, the commercial lipid nanopartic…
Complete pathologic response (CPR) correlates with long-term survival after perioperative chemoimmunotherapy (ChIO) in resectable non-small cell lung cancer (NSCLC). We provide a multiomic characterization of B cells and tertiary lymphoid structures (TLS) to dissect the immune landscape associated w…
Antigen-induced IL-12 potentiates piggyBac-engineered HER2-CAR-T cells against gastric cancer.
2026-03-04
Gastric cancer (GC) often progresses asymptomatically, resulting in late-stage diagnosis and limited therapeutic options, thus underscoring the urgent need for more effective treatments. Although chimeric antigen receptor (CAR) T-cell therapy demonstrates promise, its efficacy is frequently hindered…
The efficacy of immune checkpoint blockade (ICB) in bladder cancer (BLCA) is limited to a minority of patients. This limitation is primarily due to a non-inflamed or “cold” tumor microenvironment (TME) that lacks T-cell infiltration. Identifying the tumor-intrinsic molecular drivers and the underlyi…
Given that cancer is one of the leading causes of death worldwide, further research into new therapeutic strategies is needed. In recent years, increasing attention has been paid to the potential anticancer effects of parasitic infections and their bioactive components. Among these, the hydatid cyst…
Atopic dermatitis (AD) is a chronic inflammatory skin condition with increasing prevalence; however, the underlying immune mechanisms remain poorly understood. Precision therapeutics have shown promise, yet significant unmet clinical needs remain. Single-cell expression quantitative trait loci (sc-e…
Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of immune signaling and a target of high interest for immuno-oncology. Although numerous campaigns have been conducted to identify potent and selective HPK1 inhibitors, few encouraging clinical outcomes have been reported. Herein, we p…
Neutrophil extracellular traps (NETs) are increasingly recognized for their critical roles in tumor progression and tumor immune microenvironment (TIME) modulation, yet their functions in glioma remain incompletely understood. Leveraging 68 NET-associated regulators, we identified two distinct NET-b…
Poly (ADP-ribose) polymerase inhibitors (PARPis) benefit homologous recombination-deficient (HRD) malignancies, yet resistance remains a major challenge. Leveraging specimens from a prospective neoadjuvant niraparib monotherapy trial in treatment-naive, high-grade serous ovarian cancer, we integrate…
Colon cancer remains a therapeutic challenge due to limited efficacy of current treatments. This study investigates the synergistic antitumor effects of cordycepin combined with CTLA-4 inhibitors, focusing on their ability to reshape the gut microbiome. By integrating multi-omics approaches, we eluc…
Smoking is the most significant preventable cause of lung cancer, influencing both tumor progression and the circulating nucleic acid milieu. Consequently, the interpretation of liquid biopsy signals requires a specific approach. The literature search was conducted in the PubMed and Scopus databases…
Glioblastoma multiforme remains the primary brain tumor with the highest mortality rate, which is highly resistant to aggressive conventional therapies, owing to its capacity to evade the central nervous system’s distinctive immunological barriers. Several mechanisms confer this tumor resistance, su…
The prevalence of metastatic bone disease continues to rise with advances in cancer diagnostics and systemic therapy. Accurate survival prediction remains essential for surgical decision-making near the end of life. The Katagiri score is a widely used tool incorporating primary tumor histology group…
On March 28, 2025, the U.S. Food and Drug Administration (FDA) approved durvalumab (Imfinzi, AstraZeneca) with gemcitabine and cisplatin as neoadjuvant treatment, followed by single-agent durvalumab as adjuvant treatment following radical cystectomy (RC), for adults with muscle-invasive bladder canc…
Cell Therapies and Bispecific Engagers: Redefining Strategies against Checkpoint Resistance.
2026-04-15
Most patients with solid tumors either never benefit from immune checkpoint inhibitors (ICI) or relapse after an initial response, underscoring the need for additional therapies. Clinical and translational evidence points to two complementary strategies to overcome ICI resistance: redirection of eff…
Immunotherapy (IT) is widely used across multiple cancer types, yet its impact on second primary cancers (SPC) remains poorly understood. It is unclear whether IT enhances immune surveillance that prevents progression of preclinical malignancies into clinically apparent cancers….
Tertiary lymphoid structures (TLS) are associated with improved survival and enhanced response to anticancer immunotherapy. This study aimed to develop a CT imaging-based approach for noninvasive assessment of TLSs and immunotherapy response….
Oncogenic RAS drives an immunosuppressive tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC). Inhibition of RAS signaling, as is now possible with an ever-increasing pharmaceutical portfolio, not only directly blocks tumor cells but also reverses immunosuppression, enabling infiltrati…
Chimeric antigen receptor (CAR) T-cell therapy offers a promising approach to improve outcomes for patients with relapsed, refractory, or metastatic osteosarcoma. However, novel target antigens are needed to overcome obstacles limiting CAR T-cell efficacy against osteosarcoma and other solid tumors….
Many patients with muscle-invasive bladder cancer (MIBC) are ineligible for cisplatin-based therapy. We conducted a phase II trial of neoadjuvant nivolumab ± ipilimumab for cisplatin-ineligible patients….
Trop-2.2-Directed Radioimmunotherapy with 177Lu, 225Ac, and 212Pb in a Pancreatic Cancer Model.
2026-04-15
Trophoblast cell surface antigen-2 (Trop-2) is a membrane-bound antigen associated with cancer invasiveness and poorer patient outcomes. Delivery of therapeutics via Trop-2 targeting antibody-drug conjugates (ADC) has proven to be a viable and FDA-approved model. However, in the clinic, ADC dosing i…
Although surgical resection is an effective intervention for early-stage hepatocellular carcinoma (HCC), postoperative recurrence remains a major clinical hurdle. Delving into the mechanisms underlying relapse and pinpointing potential therapeutic targets are imperative for improving outcomes for pa…
CD46 is highly expressed across multiple cancer types, including prostate cancer and multiple myeloma. We have developed CD46-targeting antibody-drug conjugate (ADC) and actinium-225 (225Ac)-based α particle therapy agents that demonstrated a tumor-selective therapeutic effect. We hypothesized…
The immunosuppressive tumor microenvironment (TME) enables cancer cells to evade clinical immunotherapies. Neural networks are vital components of the TME, and interactions among cancer cells, neuronal cells, and immune cells mediate immunosuppression. Hence, understanding the mechanisms of intercel…
Chimeric antigen receptor (CAR) T-cell therapy enables potent, antigen-specific immune responses and has demonstrated success in treating hematologic malignancies. However, conventional ex vivo CAR T manufacturing remains costly, individualized, and logistically complex, posing significant barriers …
In clinical practice, patients with unresectable stage III non-small cell lung cancer (NSCLC) often exhibit limited tolerance to concurrent chemoradiotherapy (cCRT). This retrospective study evaluated the efficacy and safety of induction chemoimmunotherapy followed by definitive radiotherapy (RT) an…
What is this summary about?This is a summary of a clinical study called CheckMate 9DW. The study was published in a medical journal called The Lancet in May 2025. In this study, researchers looked at a type of liver cancer called hepatocellular carcinoma (or HCC for short). The study focused on HCC …
Cancers of the oesophagus, gastroesophageal junction (GEJ), and proximal stomach share epidemiological, molecular, and therapeutic characteristics. Despite their similarities, treatment guidelines vary, and the classification of GEJ tumours remains debated. While multiple meta-analyses have addresse…
Longevity
The last decade has seen Promethean advances in cardiac xenotransplantation, led by genetic editing of porcine xenografts, such that they lack the most immunogenic antigens. Nonetheless, cardiac xenotransplants have reached an apparently insuperable survival limit of around 50 days. Immunity …
With population aging, the incidence of osteoporosis continuously elevates worldwide, resulting in increased fracture risks and clinical demand for orthopedic fixation. However, under osteoporotic conditions, the stability and longevity of implants are severely compromised by the pathological microe…
Mitochondria
Dysregulated tricarboxylic acid (TCA) cycle activity is increasingly recognized as a contributor to Alzheimer’s disease (AD) pathogenesis, yet the mechanistic underpinnings of the relationship remain unclear. Here, we identify isocitrate dehydrogenase 1 (IDH1), a key enzyme in the TCA cycle, as a cr…
Acute kidney injury (AKI) and chronic kidney disease (CKD) are major contributors to global morbidity and mortality, with limited treatment options beyond supportive care. Mitochondrial dysfunction is a shared feature of both conditions, driving impaired energy production, oxidative stress and cell …
In recent years, numerous studies have revealed that dysregulation of mitochondria-organelle interactions is a common feature underlying various pathological processes and pathogen infections. For instance, in Alzheimer’s disease (AD), dysfunction of mitochondrial-associated ER membranes (MAMs) lead…
Coenzyme Q10 (CoQ10) is a lipid-soluble redox cofactor essential for mitochondrial electron transport, membrane stabilization, and antioxidant defense in its reduced form. Broad clinical utility has been hampered by poor oral bioavailability and low tissue uptake using nutraceutical formulations. BP…