Exosomes are a novel class of intercellular signal modulators that contain a wide range of molecules and deliver information between cells and tissues. MicroRNAs (miRNAs), a type of regulatory non‐coding RNA, are often incorporated into exosomes as signaling molecules. In this review, we discuss the expression of exosomal miRNAs from diverse origins such as tumor cells, solid tumor tissue, and biological fluids in various cancers (lung, breast, colorectal, liver, stomach, and pancreatic). We address the biological functions of exosome‐derived miRNAs in processes such as tumor‐cell proliferation, angiogenesis, metastasis, and chemoresistance in the tumor microenvironment. In particular, we discuss three oncogenic miRNAs, miR‐21, miR‐141, and miR‐451, which occur within exosomes, in terms of gene regulation and intercellular communication. We consider therapeutic miRNA‐based nanoparticles, which are widely expressed in tumors and show promise in drug therapy. The review assesses the wide‐ranging evidence for using exosomal miRNAs as tumor markers in molecular diagnosis. Further, we consider the use of nanoparticle platforms to transport miRNAs, in the targeted treatment of disease and tumors.
T cell factor‐1 (TCF‐1) (encoded by the TCF7 gene) is a transcription factor that plays important role during the T cell development and differentiation for T cell to exercise its functions including producing memory T cells. Not only TCF‐1 can modulate the T cell development but also exerts various effects on the differentiation and function of mature CD8 + T cells. In addition, it drives the production and maintenance of the immune response of CD8 + T cells after PD‐1 checkpoint blockade therapy. TCF‐1 can serve as a potential target of immunotherapy and may provide promising novel treatment strategies for patients with cancer and infections. Moreover, TCF‐1 is a potential biomarker of CD8 + T cell functionality to predict the efficacy of immunotherapy in fighting against cancer and infections. Herein, we summarize the role of TCF‐1 in T cell development and its applications in the treatment of cancer and infectious diseases.
18 January 2025 in European Journal of Medicinal Chemistry
Cytotoxic CD4 + T cells (CD4 + CTLs) have been identified as a specialized effector population characterized by potent cytotoxic machinery, including granzymes, perforin, and the Fas/FasL pathway, that enables the direct killing of MHC-II-expressing target cells. In addition to their classical helper function, CD4 + CTLs exhibit remarkable functional plasticity, which is dynamically influenced by a multilayered regulatory network integrating intrinsic transcriptional programs, extrinsic immune checkpoints, and tissue-specific microenvironmental signals. This context-dependent behavior makes CD4 + CTLs a double-edged sword in human health and disease. CD4 + CTLs are involved in protective immunity against viruses, tumors, and in eliminating senescent cells .However, they can also contribute to immunopathology in conditions such as autoimmune diseases, fibrotic disorders, atherosclerosis, and allograft rejection. Although advances in single-cell technologies have revealed the heterogeneity and TCR repertoire features, applying this knowledge to develop safe and effective therapies continues to be a significant challenge. Major obstacles include inherent plasticity, phenotypic instability, risk of off-target effects, and discrepancies between preclinical models and human diseases. This review highlights recent advances in understanding the development, regulation, and effector functions of CD4 + CTLs, while also addressing the limitations and challenges in targeting them therapeutically. Ultimately, this perspective positions CD4 + CTLs as both targets for intervention and tools for immunotherapy.