Antibody–drug conjugates (ADCs) are a promising cancer therapy for targeted delivery of drugs to tumor cells. However, resistance to ADCs remains a challenge, necessitating the exploration of combination therapies. A strong biological theory suggests that ADCs interact with cancer cells and immune cells by triggering mechanisms such as immunogenic cell death, dendritic cell activation, and memory T-cell activation, resulting in long-term anti-tumor immunity and ultimately potential synergistic effects with immunotherapy. Based on extensive and reliable preclinical data, several clinical trials are currently combining ADCs with immune checkpoint inhibitors (ICIs) for the treatment of various cancers, including breast, gastric, and non-small-cell lung cancers, to evaluate the safety and anti-tumor activity of the combination therapy. Preliminary evidence from early clinical trials has reported more effective efficacy data. This paper reviews the combination of ADCs and immunotherapy, highlights the key mechanisms by which the two act synergistically, and summarizes the available clinical evidence against different ADCs targets. The paper also explores the re-challenges used for combination therapies and optimized design options for ADCs drugs.

The NLRP3 inflammasome, a key regulatory component in the innate immune system, bridges pathogen recognition to chronic disease pathogenesis by modulating pyroptosis, inflammatory factor release, and metabolic homeostasis. Its central role in inflammatory cascades has positioned it as a prime therapeutic target. This review delineates the NLRP3 inflammasome’s pathological contributions to multisystem disorders—spanning neurological, cardiovascular, respiratory, gastrointestinal, urological, endocrine, and rheumatological immune diseases—while systematically evaluating associated therapeutic strategies. Furthermore, we consolidate the classical activation pathways of this molecular complex and discuss targeted inhibition approaches against both the NLRP3 inflammasome and its downstream effectors. Collectively, this work establishes a critical framework for understanding disease mechanisms and advancing translational interventions.

Neutrophil Extracellular Traps (NETs) are fibrous web-like structures released by neutrophils in response to pathogenic infections or inflammatory stimuli. Composed of decondensed chromatin DNA, histones, and granular proteins, NETs primarily function to eliminate pathogens through physical entrapment and biochemical cytotoxicity. However, they may also contribute to the pathogenesis of inflammatory diseases. While NETs played an important role in pathogen defense, their non-specific components can also damage surrounding tissues, exacerbating inflammation. The role and mechanisms of NETs in various diseases have been well-documented, including autoimmune diseases, cancer, and infectious diseases. This review aims to elaborate on the mechanisms by which NETs mediate sterile inflammation.

Exercise interventions are beneficial for reducing the risk of age-related diseases, including amyloidosis, but the underlying molecular links remain unclear. Here, we investigated the protective role of interval exercise training in a mouse model of age-related systemic apolipoprotein A-II amyloidosis (AApoAII) and identified potential mechanisms. Mice subjected to 16 weeks of exercise showed improved whole-body physiologic functions and exhibited substantial inhibition of amyloidosis, particularly in the liver and spleen. Exercise activated the hepatic p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway and the downstream transcription factor tumor suppressor p53. This activation resulted in elevated expression and phosphorylation of heat shock protein beta-1 (HSPB1), a chaperone that defends against protein aggregation. In amyloidosis-induced mice, the hepatic p38 MAPK-related adaptive responses were additively enhanced by exercise. We observed that with exercise, greater amounts of phosphorylated HSPB1 accumulated at amyloid deposition areas, which we suspect inhibits amyloid fibril formation. Collectively, our findings demonstrate the exercise-activated specific chaperone prevention of amyloidosis, and suggest that exercise may amplify intracellular stress-related protective adaptation pathways against age-associated disorders, such as amyloidosis.

Amyloidosis is a group of diseases characterized by protein misfolding and aggregation to form amyloid fibrils and subsequent deposition within various tissues. Previous studies have indicated that amyloidosis is often associated with oxidative stress. However, it is not clear whether oxidative stress is involved in the progression of amyloidosis. We administered the oxidative stress inhibitors tempol and apocynin via drinking water to the R1.P1-Apoa2^cmouse strain induced to develop mouse apolipoprotein A-II (AApoAII) amyloidosis and found that treatment with oxidative stress inhibitors led to reduction in AApoAII amyloidosis progression compared to an untreated group after 12 weeks, especially in the skin, stomach, and liver. There was no effect on ApoA-II plasma levels or expression ofApoa2mRNA. Detection of the lipid peroxidation markers 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) revealed that the antioxidative effects of the treatments were most obvious in the skin, stomach, and liver, which contained higher levels of basal oxidative stress. Moreover, the unfolded protein response was reduced in the liver and was associated with a decrease in oxidative stress and amyloid deposition. These results suggest that antioxidants can suppress the progression of AApoAII amyloid deposition in the improved microenvironment of tissues and that the effect may be related to the levels of oxidative stress in local tissues. This finding provides insights for antioxidative stress treatment strategies for amyloidosis.