Myasthenia gravis (MG) is a chronic autoimmune disorder of the neuromuscular junction characterized by fluctuating skeletal muscle weakness. Although the pathogenic roles of autoantibodies targeting the acetylcholine receptor (AChR), muscle-specific kinase (MuSK), and certain neuromuscular junction proteins have been well established, increasing evidence indicates that MG onset, progression, and therapeutic response can be shaped by the complex interactions within diverse immune microenvironments. Particularly, population heterogeneity, including differences in antibody subtype, age, sex, genetic susceptibility, ethnicity, thymic pathology, and potential confounders related to differences in healthcare conditions, strongly contributes to variability in its clinical manifestations and targeted therapies. This review discusses current evidence on the roles of the immune microenvironment and individual heterogeneity in shaping the pathogenesis and treatment landscape of MG. Along with the contributions of immunophenotyping, multi-omics techniques, single-cell and spatial transcriptomics, and biomarker discovery in improving our understanding of MG mechanisms, we also evaluated the implications of immune diversity in various populations for established therapies, as well as emerging immune-modulating approaches. This review highlights current knowledge gaps and future research priorities, emphasizing the transition from phenotype-based disease classification toward immune endotype-driven precision medicine within population heterogeneity.
Xia Xue, Chang Liu, Chunjing Qiu et al.· Frontiers in Immunology· 0 citations
Tumor-associated fibrosis is a pervasive hallmark of solid malignancies that remodels tissue architecture, biochemical signaling, and mechanical properties, thereby profoundly influencing antitumor cellular immunity across cancers. This review summarizes current understanding of the cellular and molecular drivers of fibrotic tumor stroma, highlighting heterogeneous cancer-associated fibroblast (CAF) types (myCAF, iCAF, apCAF), myofibroblasts, vascular cells and infiltrating immune cells. We further discuss the altered extracellular matrix (ECM) landscape characterized by excessive deposition and remodeling of collagens I/III, fibronectin, hyaluronan, proteoglycans, and matrix-regulating enzymes such as LOX and MMPs that collectively define desmoplasia. Particular attention is given to the signaling pathways, epigenetic programs, and metabolic regulators that initiate and sustain fibrogenesis, with the bidirectional crosstalk among tumor cells, CAFs, and immune populations that shapes immune exclusion, dysfunction, and therapeutic resistance. In addition, we review emerging experimental models and spatial multi-omics and single-cell evidence linking stromal states with immune phenotypes across pan-cancer settings. Preclinical and translational studies demonstrate that targeted ECM remodeling, CAF reprogramming, and inhibition of profibrotic signaling pathways can restore immune infiltration and enhance antitumor immunity in a context-dependent manner. This review provides a comprehensive framework for understanding how tumor-associated fibrosis regulates cellular immunity across cancers and offers insights into the development of fibrosis-targeted immunotherapeutic strategies.
