Lactic acid (LA) has transitioned from being perceived as a mere glycolytic waste product to a pivotal regulator of tumor–immune crosstalk. Historical milestones—from Scheele’s 1780 isolation from sour milk to Zhao’s 2019 discovery of histone lactylation—reveal an expanding biochemical repertoire that now encompasses pH control, G-protein-coupled receptor (GPR81/132) signaling, post-translational modification via lysine lactylation, and multi-directional metabolic shuttling between cytoplasm, mitochondria, and neighboring cells. Within the tumor microenvironment (TME), high glycolytic flux exports lactate and protons through monocarboxylate transporter 4 (MCT4), acidifying the extracellular milieu to ~6.5–6.8. This acidity degrades extracellular matrix, blunts drug uptake, and, via protonation, neutralizes weak-base chemotherapeutics. Cancer cells exploit the same molecule as fuel: MCT1-mediated uptake drives tricarboxylic acid cycle oxidation, NADPH generation via IDH1, and lactylation of DNA-repair proteins NBS1 and MRE11, enhancing genomic stability and chemoresistance. Concurrently, GPR81-cAMP-PKA-TAZ/TEAD signaling elevates PD-L1 expression, facilitating immune escape.

HOXB13, a B-class homeobox transcription factor, sits at the hub of developmental gene networks yet has emerged as a double-edged sword in human cancer. While indispensable for embryonic patterning and androgen-dependent organogenesis, its expression is frequently hijacked or extinguished by epigenetic, mutational and post-translational events that drive tumour initiation, progression and therapy resistance. Across more than twenty malignancies, the protein acts as either oncogene or tumour suppressor, depending on tissue context, interacting partners and mutational status.

Flinders University and Flinders Medical Centre researchers have found a critical link between having two types of polyps, common growths found in the bowel, and an increased risk of developing cancer, according to a new study published in Clinical Gastroenterology and Hepatology (CGH) journal.

The use of immune checkpoint inhibitors (ICIs) has significantly improved the efficacy of cancer therapy, but their associated immune-related adverse events (irAEs) can severely compromise treatment safety. This review systematically summarizes the core mechanisms underlying irAEs, which include multi-organ damage resulting from T-cell dysfunction, B-cell-mediated autoantibody abnormalities, cytokine network dysregulation, and monocyte-driven inflammatory cascades. Identified risk factors encompass a range of elements, including host clinical characteristics and underlying diseases, gut microbiota dysbiosis, characteristics of the treatment regimen, tumor type and its histological features, genetic factors and immunogenetic polymorphisms, pre-existing autoimmune conditions or a history of autoimmunity, and a history of previous exposures alongside various environmental factors. The grading criteria, their clinical context and incidence rates, and clinical management strategies for irAEs affecting various organ systems are detailed herein. Future research should aim to deeply analyze the shared mechanisms and temporal dynamics between irAEs and anti-tumor effects, develop targeted irAE prediction and monitoring systems, and optimize strategies for irAE prevention and treatment.

A new discovery by Van Andel Institute scientists reveals that glucose, an essential cellular fuel that powers immune cells, also aids in T cells’ internal communication and boosts their cancer-fighting properties. The findings may help optimize T cells’ ability to combat cancer and other diseases.

Chinese researchers have identified key immune checkpoints on natural killer (NK) cells that enable tumors to evade immune destruction. This systematic review reveals how inhibitory receptors like TIGIT, NKG2A, and PD-1 suppress NK cell function in the tumor microenvironment, and demonstrates that blocking these checkpoints – through monoclonal antibodies, gene editing (CRISPR-Cas9), or engineered CAR-NK cells – significantly enhances anti-tumor immunity. The findings provide a roadmap for next-generation immunotherapies targeting solid tumors and blood cancers.

The 48th Annual UNC Lineberger Scientific Symposium, is a day-and-a-half meeting exploring advances across the cancer research continuum—from molecular discovery to clinical application to population impact—that are improving cancer outcomes. The meeting features 16 talks by leaders in cancer research that bridge basic, translational and population sciences.

New research has revealed that perilipin 2 protein modulates aggressive cancer progression in advanced lung adenocarcinoma, the most common type of lung cancer, by regulating lipid droplet accumulation, which plays an important role in lipid metabolism by making cancer cells store more fat, acting as a fuel source. Findings from this new study in The American Journal of Pathology, published by Elsevier, suggest that perilipin 2 could serve as a prognostic factor to help predict the likely outcome (prognosis) of the disease and point to new potential lipid-based targets for treating lung adenocarcinoma.