Sex bias and association with smoking history identified in the landscape of driver mutations and clonal expansions in normal human bladder tissue may explain the higher bladder cancer risk in men and smokers.

Count Me In’s legacy of data and resources will usher in a new way of doing research on other diseases and continue to fuel cancer studies around the globe.

Rokan et al. evolved mouse melanoma to bypass immune barriers, making it transplantable. Transplantable tumors activated antiviral signals and blocked immune attack. Similar traits appear in some human melanomas, helping us understand how cancer evades immune detection and the histocompatibility barrier.

An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and develop...

Fan et al. discovered that local cardiac injury triggers aberrant lysozyme 2 (Lyz2) expression in remote zones. Lyz2 acts as a remote-injury-triggered regulator of lysosomal degradation in endocardial cells, driving pathogenic extracellular matrix breakdown. Inhibiting the LYZ2-mediated injury response—via knockout or pharmacological lysosomal inhibition—confers rapid functional recovery of non-regenerative hearts.

During paracellular transmigration, neutrophils exit the vasculature not through simple endothelial retraction but via dynamic membrane tunnels formed by overlapping endothelial cells. Using high-resolution live imaging, the authors et al. reveal that neutrophils actively remodel endothelial membranes to create 3D exit tunnels.

An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and develop...

Tumor-associated macrophages (TAMs) are key regulators of the tumor microenvironment (TME), but their heterogeneity, driven by tumor-derived cues, poses challenges for therapeutic targeting and underscores the need for precise macrophage reprogramming strategies. Through a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screen, Marelli et al. identified chemosensors as lipid-sensing regulators of macrophage activity, revealing new therapeutic avenues.

In this issue of Cancer Cell, Chen et al. identify DNASE1L3-expressing dendritic cells (DCs) as enhancers of anti-tumor immunity. By degrading neutrophil extracellular traps, these DCs promote CD8⁺ T cell infiltration into tumors and enhance checkpoint blockade efficacy, extending DNASE1L3’s known immune regulatory role to physical remodeling of the tumor microenvironment.

Treatment resistance limits long-term effectiveness in cancer therapy. Conventional biomarkers typically rely on static gene expression levels. In this issue of Cancer Cell, Jassim et al. report a new approach, RECODR, which captures how gene relationships shift over time, uncovering hidden drivers of resistance and suggesting effective combination treatments.

Phagocytes initiate immunity to invading microorganisms by detecting pathogen-associated molecular patterns via pattern recognition receptors. Pathoge…

Autoimmune diseases arise from genetic and environmental factors that disrupt immune tolerance. Recent studies highlight the role of myeloid cell immunometabolism, particularly mitochondrial dysfunction, in driving autoimmunity. Mitochondria regulate energy homeostasis and cell fate; their impairment leads to defective immune cell differentiation, abnormal effector activity, and chronic inflammation. We propose that chronic metabolic stress reprograms myeloid cells, fueling a vicious cycle of cell death and immune activation. Over time, this may induce several states of maladaptation in myeloid cells. Viewing autoimmune disease through a metabolic lens offers new insight into disease mechanisms and highlights potential therapeutic opportunities targeting mitochondrial function to restore immune balance.