bims-exocan 2026-03-15 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2026–03–15
seven papers selected by
Muhammad Rizwan, COMSATS University

Prognostic prediction and immune microenvironment analysis in colorectal cancer using exosome-related lncRNA signatures.
Polarization-Specific Macrophage-Derived Extracellular Vesicles: Molecular Cargo, Tumor Microenvironment Remodeling, and Therapeutic Opportunities.
Tumor-Derived Exosomal TAGLN2 Promotes Metastasis by Inducing Vascular Permeability and Angiogenesis via the NRP1/SEMA4D/YAP Axis.
Understanding the role of regulatory T cell-derived small extracellular vesicles in suppression of anti-tumor immune response: Key to advancing cancer immunotherapy.
ABA-Induced Cargo Proteins Loading in Extracellular Vesicles for Gene Editing.
Extracellular Vesicles in Cancer Diagnosis and Therapy: Advances, Challenges, and Prospects for Clinical Translation.
Exosomal cannabidiol: A promising candidate for targeted oral delivery against breast cancer.

Discov Oncol. 2026 Mar 10.

Prognostic prediction and immune microenvironment analysis in colorectal cancer using exosome-related lncRNA signatures.

Haohui Li, Xiaoping Huang, Zhenchao Luo, Fangfang Zhou, Yunyao Deng, Canliang Tan, Yiyi Jin, Jian Yan, Gang Xiao.

   BACKGROUND: Exosomes play a crucial role in tumor microenvironment (TME) by mediating cell-cell communication, but their role in colorectal cancer (CRC) remains unclear. This study aimed to investigate exosome-related lncRNAs (ER-lncRNAs) in CRC.
METHODS: mRNA profiles and clinical data from TCGA and GEO, microbiome data from TCMAand exosome-related genes from ExoCarta were analyzed. Consensus clustering, ER-lncRNA-related risk signature, and nomogram were developed.
RESULTS: A total of 797 differentially expressed lncRNAs (DE-lncRNAs)were identified, with 490 ER-lncRNAs selected based on their correlation with exosome-related mRNAs. Consensus clustering stratified CRC samples into four molecular subtypes, with Cluster 2 exhibiting the most favorable prognosis and Cluster 1 the poorest. These subtypes showed significant differences in survival outcomes, immune cell infiltration, and therapeutic responses. Nine ER-lncRNAs were identified as prognostic biomarkers and used to develop a risk score model. Furthermore, a nomogram incorporating the risk score and clinical parameters was constructed to predict individual prognosis.
CONCLUSION: These findings highlight the clinical relevance of ER-lncRNAs as in CRC and underscores their potential as novel diagnostic and therapeutic targets.

Keywords:  Colorectal cancer; Exosome; IncRNAs; Prognosis; Tumor microenvironment

DOI:  https://doi.org/10.1007/s12672-026-04755-1
Int J Nanomedicine. 2026 ;21 587735

Polarization-Specific Macrophage-Derived Extracellular Vesicles: Molecular Cargo, Tumor Microenvironment Remodeling, and Therapeutic Opportunities.

Xudong Liu, Yan Yang, Lu Ren.

  Extracellular vesicles (EVs) derived from macrophages have emerged as critical regulators of tumor progression by functioning as polarization-dependent carriers of bioactive molecular information. Rather than acting as passive byproducts, macrophage-derived EVs reflect the activation state of their parent cells and actively reprogram tumor behavior and the tumor microenvironment. In this review, we propose a conceptual framework in which macrophage-derived EVs serve as information hubs that link macrophage polarization, selective cargo loading, and coordinated modulation of tumor and immune cell phenotypes. EVs released from classically activated (M1) macrophages predominantly convey tumor-suppressive signals, including specific noncoding RNAs and immunomodulatory proteins, thereby inhibiting tumor proliferation, invasion, immune evasion, and therapeutic resistance while reinforcing anti-tumor immunity. In contrast, EVs derived from alternatively activated (M2) macrophages deliver a coherent pro-tumor program that integrates epithelial-mesenchymal transition, metabolic reprogramming, stemness maintenance, ferroptosis resistance, immune suppression, and therapy tolerance across multiple cancer types. We systematically summarize the emerging mechanisms governing polarization-dependent cargo selection, including RNA-binding protein-mediated sorting, metabolic and signaling pathway control, and EV biogenesis regulation. In addition, this review highlights the translational implications of macrophage-derived EVs as engineering-ready platforms. We discuss strategies to enhance the therapeutic utility of M1 EVs through cargo engineering and surface functionalization, as well as approaches to disrupt, reprogram, or selectively block M2 EV-mediated oncogenic information flow. Collectively, this work advances a unifying molecular and translational perspective, positioning macrophage-derived EVs as actionable targets and tools for precision modulation of the tumor microenvironment in cancer diagnosis and therapy.

Keywords:  TAM; exosomes; extracellular vesicles; macrophages; tumor

DOI:  https://doi.org/10.2147/IJN.S587735
Adv Sci (Weinh). 2026 Mar 13. e21962

Tumor-Derived Exosomal TAGLN2 Promotes Metastasis by Inducing Vascular Permeability and Angiogenesis via the NRP1/SEMA4D/YAP Axis.

Shuqi Yu, Jiajia Zhuo, Xiaoquan Hong, Shihao Rao, Yafang Ye, Dandan Kang, Huifang Peng, Huiqin Zhuo.

  Tumor-derived exosomes critically mediate metastasis, yet how specific cargoes reprogram the vasculature remains unclear. In gastric cancer (GC), we identify TAGLN2 as a key exosomal mediator. It is co-overexpressed in GC cells and tumor-associated endothelial cells (TECs), and its high endothelial expression correlates with lymph node metastasis and poor prognosis. Functionally, GC-derived exosomes deliver TAGLN2 to endothelial cells (ECs), orchestrating angiogenesis, EndoMT, and the disruption of endothelial junctions. In vivo, exosomal TAGLN2 accelerated tumor growth and lung metastasis by generating abnormal, leaky vasculature and hypoxia. Mechanistically, exosomal TAGLN2 initiates a novel signaling axis: it transcriptionally upregulates NRP1 via c-Jun/SP1 and concurrently induces SEMA4D expression. TAGLN2 then interacts with both NRP1 and SEMA4D to nucleate a stable cytoplasmic ternary complex. This complex dually activates YAP by competitively disrupting NRP1-YAP binding to release YAP from cytoplasmic retention, and simultaneously suppressing Hippo-mediated degradation, operating independently of the canonical SEMA4D-PlexinB1-RhoA/ROCK pathway. Therapeutically, targeting the TAGLN2 axis synergized with both cisplatin and bevacizumab, potently suppressing tumor progression by impairing neovascularization and promoting vascular normalization. Clinically, exosomal TAGLN2 levels were significantly elevated in GC patient serum. Our study delineates a complete exosome-to-vasculature signaling axis and positions TAGLN2/NRP1/SEMA4D/YAP module as an integrated diagnostic and therapeutic target against metastatic GC.

Keywords:  angiogenesis; exosomal TAGLN2; gastric cancer; metastasis; vascular permeability

DOI:  https://doi.org/10.1002/advs.202521962
Int Rev Immunol. 2026 Mar 11. 1-23

Understanding the role of regulatory T cell-derived small extracellular vesicles in suppression of anti-tumor immune response: Key to advancing cancer immunotherapy.

Pranav Seth, Subrata Kumar Pore, Sonja Ludwig, Priyanka Sharma.

  Regulatory T cells (Tregs) represent a distinct T cell subpopulation crucial for preserving immune homeostasis. Their primary function is to facilitate self-tolerance and suppress other immune responses, achieved through multifaceted mechanisms, including the secretion of extracellular vesicles (EVs) such as exosomes, which effectively modulate the activity of other innate and adaptive immune cells. Treg-derived extracellular vesicles (Treg-EVs) are minute, membrane-bound vesicles containing specific biological molecules, comprising proteins, nucleic acids, and lipids. Upon transfer to target cells, these molecules exert diverse effects on immune responses. The Treg-mediated immune suppression process encompasses several contact-dependent and contact-independent mechanisms. These encompass the expression of various inhibitory receptors, such as CTLA-4, PD-1, CD39, and CD73, which serve to regulate the immune response. Furthermore, Tregs exhibit the capacity to directly eliminate target cells through the expression of perforin and granzyme B. Additionally, Tregs produce immunosuppressive cytokines that play a pivotal role in maintaining immune system equilibrium. Studying the impact of Treg-derived exosomes on the immune system in cancer is crucial for advancing cancer research and treatment. Understanding these interactions is vital for unraveling the potential implications for cancer development and progression.

Keywords:  Cancer progression; cytokines; exosomes; immune suppression; membrane-bound vesicles; regulatory T cells

DOI:  https://doi.org/10.1080/08830185.2026.2631464
Cells. 2026 Feb 26. pii: 405. [Epub ahead of print]15(5):

ABA-Induced Cargo Proteins Loading in Extracellular Vesicles for Gene Editing.

Sai Wei, Jian Li, Huacan Tuo, Wei Wang, Guo Li, Luan Wen.

  Extracellular vesicles, which carry bioactive cargos such as proteins, RNAs, and lipids, represent promising drug delivery vehicles owing to their biocompatibility, low immunogenicity, and inherent tissue-targeting capabilities. To address the current limitations in controlled cargo loading, we developed an abscisic acid (ABA)-inducible proximity system that directs proteins into exosomes during biogenesis. We engineered exosomal scaffolds by fusing the ABA receptor PYL1 to EV-enriched proteins-including BASP1, CD9, PTGFRN, and a truncated form PTGFRNΔ687-thereby creating docking sites within the exosomal lumen, while the target cargo (e.g., EGFP, firefly luciferase, or Cas9) was tagged with the ABI1 phosphatase domain. We demonstrate that ABA administration in producer cells induces PYL1-ABI1 complex formation, which recruits ABI1-fused cargo for selective encapsulation into EVs. Among the scaffolds tested, BASP1-PYL1 proved the most effective, enabling robust, ABA-dependent enrichment of cargo proteins. Purified EVs maintained canonical morphology, size, and marker expression (CD63, syntenin-1, CD9), confirming preserved biogenesis. Critically, these loaded exosomes efficiently delivered functional cargo to recipient cells, enabling Cas9/sgRNA-mediated genome editing. Together, our findings establish an ABA-triggered molecular switch for controllable EV protein loading, providing a versatile platform for next-generation therapeutic delivery.

Keywords:  Cas9; abscisic acid (ABA); chemically induced proximity; extracellular vesicles (EVs); protein loading

DOI:  https://doi.org/10.3390/cells15050405
Int J Mol Sci. 2026 Feb 28. pii: 2280. [Epub ahead of print]27(5):

Extracellular Vesicles in Cancer Diagnosis and Therapy: Advances, Challenges, and Prospects for Clinical Translation.

Lingyu Kong, Guangyu Zhao, Xinwei Wu, Shuang Ma.

  Extracellular vesicles (EVs) have emerged as promising tools for cancer diagnosis and therapy owing to their excellent biocompatibility, low immunogenicity, and ability to transport diverse bioactive molecules. This review summarizes recent advances in EVs research, focusing on isolation and detection technologies, their diagnostic and therapeutic applications in oncology, and the key challenges limiting clinical translation. Conventional EVs isolation methods, including ultracentrifugation, density-gradient centrifugation, and polymer-based precipitation, are discussed alongside emerging strategies such as immunoaffinity enrichment, microfluidic separation, lipid-mediated isolation, and thermophoretic enrichment, with comparative evaluation of their yield, purity, cost, and scalability. In cancer diagnosis, EV-associated biomolecules, such as miRNAs, mRNAs, proteins, and lncRNAs, show strong potential as liquid biopsy biomarkers for noninvasive early detection and dynamic disease monitoring. In therapeutic contexts, EVs serve as versatile carriers for gene molecules, chemotherapeutic agents, and small-molecule drugs, and can enhance immunotherapy and RNA-based treatments. Importantly, EVs released from metabolically active tissues, particularly skeletal muscle, contribute to systemic immune regulation and metabolic homeostasis, and their biogenesis and molecular cargo can be influenced by physical activity and exercise-related nutritional status. These insights highlight the need to integrate microengineering technologies, biomolecular profiling, standardized manufacturing systems, and lifestyle-related factors such as exercise and nutrition to accelerate the clinical translation of EV-based strategies in precision oncology and regenerative medicine.

Keywords:  cancer diagnosis; cancer therapy; exercise-related health; extracellular vesicles; liquid biopsy

DOI:  https://doi.org/10.3390/ijms27052280
Cancer Lett. 2026 Mar 09. pii: S0304-3835(26)00179-5. [Epub ahead of print]646 218416

Exosomal cannabidiol: A promising candidate for targeted oral delivery against breast cancer.

Disha Nagesh Moholkar, Raghuram Kandimalla, Jeyaprakash Jeyabalan, Richa Singhal, Katarina Mayer, Carolyn M Klinge, Ramesh C Gupta, Farrukh Aqil.

  Breast cancer (BCa) remains a leading cause of cancer-related deaths in women worldwide. Triple-negative BCa (TNBC) is highly metastatic with treatment limited by off-target toxicity. Cannabidiol (CBD) has anti-cancer and anti-inflammatory activity in BCa. This study addresses the poor oral bioavailability of CBD by utilizing exosomes (Exo) as a drug delivery system. CBD was loaded onto non-functionalized exosomes and folic acid-functionalized exosomes (FA-Exo), achieving an average CBD drug load of ∼20%. The FA-ExoCBD averaged 136 ± 2.9 nm in size. TNBC cell lines MDA-MB-231 and taxol-resistant MDA-MB-231TR were sensitive to growth inhibition by CBD than estrogen receptor positive (ER+) MCF-7 and its taxol-resistant derivative MCF-7TR. Exosomal formulations (ExoCBD and FA-ExoCBD) demonstrated time-dependent CBD release under physiologically relevant simulated gastric and intestinal conditions and withstand acidic conditions, retained canonical exosomal markers (CD81 and Alix) as well as physical parameters of exosomes including size, PDI and zeta potential. CBD downregulated key anti-apoptotic and anti-inflammatory markers. Oral FA-ExoCBD showed enhanced tumor targeting, tumor retention and inhibition of orthotopic MDA-MB-231-tumor growth in NOD Scid mice than ExoCBD or free CBD. RNA-Seq analysis of tumor tissues revealed that both CBD and FA-ExoCBD treatments modulated over 1000 genes, with FA-ExoCBD significantly downregulating IL13RA2 (associated with lung metastasis) and tumor biomarkers TRPM2 and SAMHD1, while upregulating tumor suppressors PRDM1, PCDHGB2, and ICAM1. These findings highlight the potential of FA-ExoCBD to enhance CBD's anticancer efficacy through targeted gene modulation. Overall, FA-ExoCBD improves CBD's therapeutic profile by enhancing efficacy, tumor selectivity, improved bioavailability and anticancer efficacy.

Keywords:  Breast cancer; Cannabidiol; Colostrum; Exosomes; Targeted oral delivery

DOI:  https://doi.org/10.1016/j.canlet.2026.218416