Alveolar macrophages (AMs) are immune cells located in the alveoli—the tiny air sacs in the lungs where gas exchange occurs. Their functions are regulated by various epigenetic mechanisms, which are essential for both healthy lung function and disease development. In the lung’s microenvironment, AMs play critical roles in immune surveillance, pathogen clearance, and tissue repair. This review examines how epigenetic regulation influences AM functions and their involvement in lung diseases. Key mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs, regulate gene expression in response to environmental signals. In healthy lungs, these modifications enable AMs to quickly respond to inhaled threats. However, when these processes malfunction, they could contribute to diseases such as pulmonary fibrosis, COPD, and pulmonary hypertension. By exploring how epigenetic changes affect AM polarization, plasticity, and immune responses, we can gain deeper insights into their role in lung diseases and open new avenues for treating and preventing respiratory conditions. Ultimately, understanding the epigenetic mechanisms within AMs enhances our knowledge of lung immunology and offers potential for innovative interventions to restore lung health and prevent respiratory diseases.

Regulatory T cells (Tregs) are central mediators of immune tolerance, yet within tumors they adopt specialized phenotypes that confer the potent suppression of anti-tumor immune responses. Emerging evidence indicates that this functional plasticity is not driven by genetic alterations but instead arises from dynamic and context-dependent epigenetic reprogramming. While individual epigenetic mechanisms controlling Treg development and stability have been described, how tumor-derived cues reshape Treg epigenetic states, how these programs differ across cancer types, and which features distinguish tumor-infiltrating Tregs from their peripheral counterparts remain incompletely understood. In this review, we synthesize recent advances in DNA methylation, histone modifications, chromatin accessibility, and non-coding RNA regulation that govern Treg identity and function with a particular emphasis on tumor-specific epigenetic adaptations. We highlight emerging epigenetic hallmarks of intratumoral Tregs, discuss unresolved mechanistic questions, and evaluate the therapeutic potential and limitations of targeting epigenetic pathways to selectively modulate Tregs in cancer. By integrating mechanistic, cancer-specific, and translational perspectives, this review aims to provide a conceptual framework for understanding how epigenetic regulation shapes Treg behavior in the tumor microenvironment and how it may be exploited for cancer immunotherapy.

Malignant cells hijack epigenetic processes to sustain proliferation and to tolerate stressors that would otherwise limit cell growth, yet the chromatin remodeling activities that establish and maintain these programs are poorly defined. H2A.Z is a histone variant deposited into nucleosomes by the SRCAP and TIP60 chromatin-remodeling complexes, which share VPS72 as a chaperone subunit. VPS72 is located at 1q21, a region recurrently gained in human cancers, yet its contribution to tumor biology remains largely unexplored. Here, we show that VPS72 copy-number gain occurs in more than one-third of tumors and its expression is enriched beyond that expected from neighboring 1q21 genes and remains elevated over normal tissue in copy-neutral tumors. Across cancer types, higher VPS72 expression was associated with proliferative transcriptional programs, cell-cycle–related chromatin accessibility, and genomic instability. Single-cell analyses localized these associations primarily to malignant cells. Higher VPS72 expression and copy-number gain were associated with shorter overall survival in several solid tumors, although these relationships varied by lineage. VPS72 copy-number gain was also associated with shorter overall survival after adjustment for age and sex. Cancer-cell screens further identified recurrent VPS72 dependency, and VPS72 depletion suppressed proliferative programs while inducing stress, inflammatory, and apoptotic responses that were only partly shared with H2A.Z depletion. Together, these findings identify VPS72 as a recurrently altered component of tumor chromatin regulation associated with proliferative and stress-response states and support further investigation of its therapeutic significance.

Obesity is characterized by chronic low‐grade inflammation and metabolic dysfunction. It is a major risk factor for hidradenitis suppurativa (HS), where it is associated with increased disease severity and metabolic comorbidity. Obesity promotes a pro‐inflammatory, immunometabolic state marked by adipokine imbalance and alters the local skin environment through mechanical stress, occlusion and microbiome disruption. Mechanistic transcriptomic analyses further suggest that obesity induces tissue‐specific changes in HS skin, including metabolic signalling in lesions and early barrier dysfunction in perilesional skin. In practice, obesity is associated with more severe and treatment‐refractory disease but remains a modifiable risk factor. Weight loss, bariatric surgery and metabolism‐directed therapies show potential to reduce disease burden, although controlled studies are limited. Overall, obesity acts as both a systemic and local modifier of HS, supporting its classification as an immunometabolic disorder.