Abstract. Inflammation has enduring impacts on organismal immunity. However, the precise mechanisms by which tissue-restricted inflammation conditions syst

Dijkstra et al. investigate whether individual cancer subclones differ in their immune evasion capacity. They establish organoids representing distinct subclones from multi-region lung cancer biopsies. Co-culture with T or NK cells shows heterogeneity in immune evasion across different tumor subclones, demonstrating that immune escape is shaped by subclonal evolution.

Lang et al. show that tumor-tropic mutations in lymphocytic choriomeningitis virus (LCMV) enhance selective replication in cancer cells. The optimized LCMV promotes strong and sustainable anti-tumor efficacy and T cell-mediated immunity in murine models and is well tolerated in non-human primates, supporting its potential as a safe cancer immunotherapy.

Malignant tumors are characterized by diverse metabolic stresses, including nutrient shortages, hypoxia, and buildup of metabolic by-products. To understand how cancer cells adapt to such challenges, ...

Immunotherapy as single-agent PD-1 blockade does not work for patients with microsatellite stable (MSS) colorectal cancer. In this issue of Cancer Cell, Morris et al. demonstrate that targeting the mitogen-activated protein kinase (MAPK) pathway in combination with immunotherapy can reprogram BRAF-V600E mutant MSS colorectal cancers toward immune responsiveness.

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.