bims-exocan 2025-09-07 papers

Issue of 2025–09–07
three papers selected by
Muhammad Rizwan, COMSATS University

Front Immunol. 2025 ;16 1628573

Multidimensional insights into exosomes in hepatocellular carcinoma: from genesis to clinical application.

Xiang Zhang, Cheng Zhang, Zheng Zhang, Xuan Zhang.

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy, whose progression is intimately linked to the complex dynamics of the tumor microenvironment (TME). Exosomes, once considered mere cellular waste, have emerged as pivotal mediators of intercellular communication within the TME, actively participating in the multistep development of HCC. These nanoscale vesicles play crucial roles in the initiation of precancerous lesions and, by transporting drug resistance-related molecules such as proteins and non-coding RNAs, facilitate the acquisition of resistance to chemotherapy and targeted therapies by tumor cells. Moreover, exosomes contribute to the establishment of pre-metastatic niches by remodeling distant organ microenvironments-inducing hypoxia, metabolic reprogramming, and angiogenesis-which collectively create favorable conditions for tumor cell colonization. They also modulate immune responses by inducing T-cell exhaustion, promoting macrophage polarization, and disrupting normal stromal cell functions, thereby constructing an immunosuppressive microenvironment that enables tumor immune evasion. Given their inherent biocompatibility and targeting capabilities, engineered exosomes have shown promise in cancer therapy, serving as carriers for therapeutic molecules and enabling precise drug delivery through surface modifications. Despite significant advancements, challenges remain in elucidating the in vivo regulatory mechanisms of exosomes, standardizing their isolation and purification processes, and evaluating their clinical efficacy. This review examines the multifaceted roles of exosomes in HCC, aiming to bridge mechanistic insights with precision diagnostics and pave new avenues for liver cancer treatment.

Keywords: drug tolerance; exosomes; hepatocellular carcinoma (HCC); metastasis; targeted therapy; tumor microenvironment (TME)

DOI: https://doi.org/10.3389/fimmu.2025.1628573

Adv Exp Med Biol. 2025 ;1485 181-196

Circular RNA in Exosomes and Its Clinical Significance.

Mohammad Kamalabadi Farahani, Sepehr Zamani, Seyede Salehe Attari.

Circular RNAs (circRNAs) are highly conserved novel class of endogenous noncoding RNAs. CircRNAs have a stable covalently closed ring structures with no 5'-end cap or 3'-end poly (A) tail. These circular structures are formed by reverse splicing, mainly by means of a noose structure or intron complementary pairing. In clinical applications of cells, exosomes, as a tiny discoid vesicles with a diameter of 40-100 nm that are secreted by cells under physiological and pathological conditions, are considered in recent years. Exosomes play an important role in cell-cell communication by carrying DNA, microRNAs, mRNAs, proteins, and circRNAs. In this chapter, we summarize the biological functions of exosomal circRNAs and further reveal the clinical significance of exosomal circRNAs and their potential roles in different diseases, providing a scientific basis for the diagnosis, treatment, and prognosis of a wide variety of diseases.

Keywords: Circular RNAs; Diagnosis; Disease biomarker; Exosomes; Prognosis

DOI: https://doi.org/10.1007/978-981-96-9428-0_12

Front Immunol. 2025 ;16 1655095

CAR-exosomes derived from immune cells: an emerging nanoscale vanguard in overcoming tumor immunotherapy hurdles.

Xiaoyan Zhao, Bin Zhao, Yan Sun, Aiguo Liu.

Chimeric Antigen Receptor (CAR)-engineered cell therapies excel against hematologic malignancies, however, their efficacy in solid tumors is hampered by toxicity, poor tumor infiltration, immunosuppressive microenvironments, limited persistence, and expansion difficulties. Recently, exosomes derived from CAR-immune cells (CAR-Exosomes) have emerged rapidly as an innovative therapeutic platform. CAR-Exosomes, utilizing nanoscale communication pathways, inherit their parental cells' tumor-targeting capabilities while offering distinct advantage. These advantages encompass low immunogenicity, enhanced tissue penetration, and versatile drug-loading capacity, presenting a promising approach to circumvent the limitations of traditional cell therapies. This review systematically summarizes the core challenges for CAR-T, CAR-NK, and CAR-M cell therapies and emphasizes recent advancements in CAR-Exosomes, including their molecular characteristics, targeted recognition mechanisms, tumor-killing pathways, biosafety, and engineering strategies. Furthermore, it also discusses the key challenges and strategies in the clinical translation of CAR-Exosomes. In conclusion, integrating nanomedicine with cell therapy, CAR-Exosomes hold significant promise as a next-generation platform aiming for high efficacy, safety, and broad clinical applicability in cancer immunotherapy.

Keywords: CAR; cancer; cell-free; exosomes; immunotherapy

DOI: https://doi.org/10.3389/fimmu.2025.1655095