bims-exocan 2026-02-15 papers

Issue of 2026–02–15
four papers selected by
Muhammad Rizwan, COMSATS University

Cancers (Basel). 2026 Feb 06. pii: 537. [Epub ahead of print]18(3):

Extracellular Vesicles in Cancer: Mechanistic Insights and Clinical Applications.

Extracellular vesicles (EVs) have emerged as important messengers in cell-to-cell communication, carrying biologically active molecules such as lipids, nucleic acids, and proteins that influence both normal physiology and disease. In cancer, EVs play complex and context-dependent roles, contributing to tumor growth, angiogenesis, immune evasion, metastasis, and resistance to therapy, while in certain settings, they may also support antitumor immune responses. Increasing evidence shows that EVs released from tumor and stromal cells actively reshape the tumor microenvironment (TME) and participate in the formation of pre-metastatic niches, thereby facilitating cancer dissemination. Because EVs are stable, readily detectable in body fluids, and reflect the molecular characteristics of their cells of origin, they have attracted considerable interest as minimally invasive biomarkers for cancer diagnosis, prognosis, and treatment monitoring. In addition, their natural biocompatibility makes them attractive candidates for targeted drug delivery. This review summarizes current knowledge on EV biogenesis, cargo composition, and functional roles in cancer progression, with a particular focus on recent advances in their clinical applications. Key challenges related to EV isolation, characterization, and clinical translations are also discussed, highlighting future opportunities for integrating EV-based strategies into precision oncology.

Keywords: biomarkers; cancer; drug delivery; extracellular vesicles; intercellular communication; liquid biopsy

DOI: https://doi.org/10.3390/cancers18030537

Autoimmunity. 2026 Dec 31. 59(1): 2628367

Exosomal circ_001895 from lung cancer cells drives M2 macrophage polarization via the miR-20a-5p/JAK1/STAT3 axis to promote tumor progression.

Zunqiao Wang, Bin Wang, Yun Gao, Jinyuan Liu, Keping Wang.

Exosomes play a vital role in cancer cell and tumor microenvironment (TME) crosstalk. M2 macrophages are major immune cells in the TME. However, the effects and molecular mechanisms by which exosomes secreted by lung cancer (LC) cells regulate macrophage polarization during tumor metastasis remain unclear. Exosomes secreted by LC cells were extracted using ultracentrifugation. Exosomes were identified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The proliferation and metastasis capacities of LC cells were detected via CCK-8 and transwell experiments. The interaction between miR-20a-5p and circ_001895 or JAK1 was subsequently confirmed through bioinformatics analysis and a luciferase reporter assay. The effect of circ_001895-induced M2 macrophages in exosomes on the metastatic ability of LC cells in vivo was verified by mouse experiments. First, we discovered that exosomes have a bilayer membrane-encapsulated vesicular structure, and the particle size is approximately 100-200 nm. LC-derived exosomes significantly promoted the growth and metastasis of LC cells. Further studies revealed that LC-derived exosomes promoted strengthened LC progression by increasing M2 macrophage polarization. Subsequently, we disclosed that circ_001895 was increased in LC tissues, cell lines, and exosome-treated macrophages. Circ_001895 stimulated M2 macrophage polarization via the miR-20a-5p/JAK1/STAT3 pathway. In vivo experiments confirmed that the LC-derived exosomal circ_001895 promoted LC progression through stimulating M2 macrophage polarization. LC-derived exosomal circ_001895 stimulated M2 macrophage polarization to promote LC metastasis via the miR-20a-5p/JAK1/STAT3 axis. These findings suggest that exosomal circ_001895 may serve as a potential biomarker and therapeutic target in lung cancer.

Keywords: LC; M2 macrophages; circ_001895; exosomes; miR-20a-5p

DOI: https://doi.org/10.1080/08916934.2026.2628367

FASEB J. 2026 Feb 28. 40(4): e71564

Exosomes: From Non-Invasive Detection to Engineered Targeted Therapy.

Mingming Sun, Hang Hu, Yi Gong.

Exosomes are naturally occurring nanovesicles present in a variety of bodily fluids that facilitate the transport of proteins and nucleic acids. Characterized by their low immunogenicity and high biocompatibility, exosomes can efficiently navigate through biological barriers. This review summarizes the applications of exosomes in disease diagnosis and treatment, emphasizing their roles as biomarkers for non-invasive detection, as well as engineered vehicles for drug delivery and vaccine development. Additionally, this review also discusses recent technological advancements in exosome engineering, including genetic modification techniques and chemical modifications aimed at optimizing targeted delivery systems and enhancing immunomodulation strategies. Notably, it highlights the significant potential of exosomes to transform non-invasive diagnostics while promoting the development of sophisticated therapeutic carriers.

Keywords: engineering strategies; exosome; non‐invasive diagnosis

DOI: https://doi.org/10.1096/fj.202504351R

Neoplasia. 2026 Feb 11. pii: S1476-5586(26)00009-6. [Epub ahead of print]73 101280

Targeting the ANXA2-CD63-exosomal PD-L1 axis in hepatocellular carcinoma: A novel mechanism of immune evasion and its implications for precision immunotherapy.

Jian Zhang, Ying Gu, Fangchao Zhao, Yong Chen, Yuqing Xia, Dekang Gao, Qiang Yuan, Xuming Bai.

BACKGROUND AND PURPOSE: Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths globally due to late diagnosis and resistance to therapies, including immune checkpoint blockade (ICB). Tumor-derived exosomes carrying programmed death-ligand 1 (PD-L1) have emerged as key mediators of immune evasion by binding PD-1 on T cells, thereby inducing T cell exhaustion and systemic immunosuppression. This study investigated whether Annexin A2 (ANXA2) modulates exosomal PD-L1 expression in HCC cells to inhibit T-cell function and promote immune escape.
RESULTS: Bioinformatic analyses (TIMER2.0, TCGA) showed ANXA2 upregulation in HCC, correlating with fewer CD8⁺ T cells and poor survival. ANXA2 knockout (KO) in Hepa1-6 cells reduced exosome secretion and exosomal PD-L1, confirmed by EM, nanoparticle tracking, and WB. Exosomes from controls suppressed CD8⁺ T cell activation (reducing CD69, IL-2, IFN-γ, TNF-α), while KO exosomes did not. ANXA2 KO tumors grew slower in immunocompetent C57BL/6 J mice but not in immunodeficient BALB/c Nude mice, highlighting immune dependence. ANXA2 depletion reduced CD63 protein stability without affecting mRNA. CD63 re-expression in KO cells restored exosomal PD-L1, indicating ANXA2 maintains CD63 stability for PD-L1 exosomal incorporation. Transcriptomic and pharmacologic evidence further supported a role for lysosome-associated turnover in CD63 loss upon ANXA2 depletion.
CONCLUSIONS: ANXA2 drives HCC immune evasion by upregulating exosomal PD-L1 via CD63 stabilization, offering a novel target to enhance ICB efficacy. This work highlights a tumor-specific exosome regulation mechanism, with potential implications for immunotherapy across exosome-dependent cancers.

Keywords: Annexin A2; Exosomal PD-L1; Hepatocellular carcinoma; Immune evasion; T-cell suppression

DOI: https://doi.org/10.1016/j.neo.2026.101280