The tumor microenvironment (TME) plays a pivotal role in shaping tumor progression, therapeutic resistance, and immune evasion. Among the diverse cellular constituents of the TME, cancer-associated adipocytes (CAAs) have gained increasing recognition as active modulators of cancer biology. Once considered passive energy reservoirs, adipocytes undergo functional and phenotypic reprogramming under the influence of tumor-derived signals, transforming into pro-tumorigenic CAAs. These altered adipocytes not only supply metabolic substrates to cancer cells but also orchestrate an immunosuppressive landscape conducive to tumor growth and metastasis. Through the secretion of adipokines, pro-inflammatory cytokines, and extracellular vesicles, CAAs influence the recruitment, differentiation, and functional polarization of immune cells such as regulatory T cells (Tregs), tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs). Additionally, CAAs contribute to extracellular matrix remodeling, hypoxia, and lipid metabolism dysregulation, all of which suppress anti-tumor immune responses. This review synthesizes current knowledge on the role of CAAs in shaping the immunosuppressive TME, with a focus on breast, ovarian, and pancreatic cancers. We also discuss emerging therapeutic strategies targeting CAAs and their immunomodulatory networks to enhance the efficacy of cancer immunotherapy.

Glioblastoma (GBM) poses a significant therapeutic challenge due to its highly immunosuppressive tumor microenvironment (TME). Current treatments, including surgery, radiotherapy, and chemotherapy, offer limited survival benefits, as the TME fosters immunological escape and tumor growth. This review analyzes the clinical limitations of current therapies, the complicated molecular mechanisms pathways driving immunosuppression in the GBM TME, and promising future solutions. We address the role of tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and the blood-brain barrier (BBB) in reinforcing immune evasion. Potential therapeutic approaches include targeting these immunosuppressive mechanisms by metabolic reprogramming, epigenetic modulation, and novel multi-modal therapies that might change treatment outcomes for GBM patients.

Ficolin-1 (FCN1, M-FCN), the key pattern recognition molecule of the innate immune system, possesses a collagen-like domain and a fibrinogen-like domain, exhibiting bidirectional immunomodulatory functions that influence immune homeostasis and disease progression. Recent studies reveal that beyond its well-established roles in pathogen recognition and complement activation, FCN1 orchestrates the balance between pro-inflammatory and anti-inflammatory responses, facilitating crosstalk between innate and adaptive immunity. This review synthesizes cutting-edge research to systematically elucidate the multifaceted roles of FCN1 in human diseases, including autoimmune disorders, infectious diseases, tumor, cardiovascular and cerebrovascular disease. We highlight how FCN1 exerts its regulatory effects through diverse mechanisms-ranging from pathogen binding and clearance to cytokine secretion modulation and immune cell fate determination-ultimately shaping disease susceptibility, progression, and prognosis. By compiling these groundbreaking findings, we propose FCN1 as a pivotal orchestrator of immune responses, providing a theoretical foundation for its translation into diagnostic biomarkers and novel therapeutic targets in precision medicine. This review advocates for the establishment of standardized FCN1 assays and large-scale clinical validation to accelerate its transformation from bench to bedside.

Summary: Metabolic reprogramming dynamically regulates antiviral defense across innate and adaptive immunity. Immune cells exert their antiviral functions by undergoing metabolic reprogramming. In this review, the significance of metabolic reprogramming of immune cells is discussed, including the effects of metabolic pathways, such as glycolysis, oxidative phosphorylation (OXPHOS), tricarboxylic acid (TCA) cycle, pentose phosphate pathway (PPP), and fatty acid oxidation (FAO) on the maturation, differentiation and function of immune cells. Furthermore, this review elaborates on the specific effects of metabolic reprogramming on various immune cell types, including T cells, B cells, macrophages and dendritic cells (DCs). It covers the metabolic changes following T cell activation and subpopulation differentiation, B cell metabolic remodeling in germinal center response, and macrophage polarization and dendritic cell immunogenicity and immune tolerance. This review summarizes the recent advance of metabolic reprogramming on the effects of the direct regulation of immunotherapy strategies, proinflammatory response, adaptive immunity, as well as the indirect regulation of adaptive immunity through innate immunity. It is worth noting that this review proposes immunotherapy strategies targeting metabolic pathways and the application of metabolic modulators in immunotherapy, and analyzes the key role of metabolic reprogramming in adaptive immune regulation, emphasizing its potential application in the treatment of inflammatory diseases.

Fixation of complement-related protein fragments occurs following treatment of Raji, a CR2-positive lymphoblastoma cell line, with NHS but not with hi-S. From the immunoblot developed by autoradiography of cells pretreated with OKB7, an anti-CR2 moAb, and subsequently treated with I 125NHS, two proteins of 60 and 74 kD were visible. These proteins should be cleavage products, components of the cell surface C3c network, poles of attraction for low m.w. molecules and thus could provide acceptor sites for the fixation of complement-related protein fragments. Indirect evidence would indicate that free C3d, or as a component of a complement protein, could be the delivery system of low m.w. molecules to highlight the surface Ag/Ab interaction sites. Flow cytometric data would suggest that Raji cells secrete or shed proteins that act as autocrine factors. They are involved in the coating and disclosing processes of C3c determinants, the detection of which is strongly inhibited by cell treatment with NHS but not by hi-S.

Hepatocellular carcinoma (HCC) represents a significant global cause of cancer-related mortality. Hepatitis B virus (HBV)infection is a major etiologic factor leading to HCC. While noteworthy progress has been made in managing HBV replication, achieving a cure for HBV-related HCC (HBV-HCC) remains challenging, and the overall survival outcome for HCC remains suboptimal. HBV persistence is attributed to a myriad of mechanisms, encompassing both innate and adaptive immune responses. Regulatory T cells(Tregs) are pivotal in upholding immune tolerance and modulating excessive immune activation. During HBV infection, Tregs mediate specific T cell suppression, thereby contributing to both persistent infection and the mitigation of liver inflammatory responses. Studies have demonstrated an augmented expression of circulating and intrahepatic Tregs in HBV-HCC, which correlates with impaired CD8 + T cells function. Consequently, Tregs play a dual role in the context of HBV infection and the progression of HBV-HCC. In this comprehensive review, we discuss pertinent studies concerning Tregs in HBV infection, HBV-related cirrhosis and HCC. Furthermore, we provide valuable treatment strategies pertinent to liver cancer management.