bims-exocan 2025-11-02 papers

Issue of 2025–11–02
five papers selected by
Muhammad Rizwan, COMSATS University

Front Immunol. 2025 ;16 1679934

Cancer-derived exosomes: mediators of immune crosstalk and emerging targets for immunotherapy.

Ridwan Mahamed, Bernice Monchusi, Clement Penny, Sheefa Mirza.

Exosomes, nanoscale extracellular vesicles secreted by various cell types, play pivotal roles in intercellular communication. In cancer, tumor-derived exosomes-referred to as cancer-derived exosomes (CDEs)-have emerged as critical regulators of immune evasion, tumor progression, and therapy resistance within the tumor microenvironment (TME). CDEs modulate immune cell function through the transfer of immunosuppressive proteins, cytokines, and non-coding RNAs, ultimately reprogramming immune surveillance mechanisms. This review provides an in-depth analysis of how CDEs influence major immune cell subsets-including T cells, B cells, NK cells, dendritic cells, macrophages, and myeloid-derived suppressor cells-thereby establishing an immunosuppressive TME. We also explore the potential of immune cell-derived exosomes (IDEs) as emerging immunotherapeutic tools capable of counteracting the suppressive effects of CDEs. Furthermore, we highlight exosome engineering strategies aimed at improving therapeutic cargo delivery, tumor targeting, and antitumor immune activation. Finally, we discuss how exosome profiling offers promise in liquid biopsy diagnostics and how integration with 3D tumor models and advanced bioengineering can accelerate the clinical translation of exosome-based cancer immunotherapies.

Keywords: cancer-derived exosomes; immune-crosstalk; immune-modulation; immunotherapy; tumor microenvironment

DOI: https://doi.org/10.3389/fimmu.2025.1679934

Cancers (Basel). 2025 Oct 21. pii: 3386. [Epub ahead of print]17(20):

Exosomes in HPV-Associated Cancers: From Biomarkers to Engineered Therapeutics.

Muharrem Okan Cakir, Melis Selek, Betul Yilmaz, Mustafa Ozdogan, G Hossein Ashrafi.

BACKGROUND/OBJECTIVES: Human papillomavirus (HPV) is the main causative agent of cervical cancer and contributes to a significant proportion of other anogenital and oropharyngeal malignancies. The need for better biomarkers and therapeutic approaches in HPV-associated cancers has drawn attention to exosomes, small extracellular vesicles known for their stability, biomolecule transport capabilities, and role in cell-to-cell communication.
METHODS: This review comprehensively evaluates recent literature on the diagnostic, prognostic, and therapeutic applications of small extracellular vesicles, particularly exosomes, in HPV-related cancers. It analyzes findings on exosomal nucleic acids, proteins, and long non-coding RNAs, as well as engineered exosome-based therapies.
RESULTS: Exosomal miRNAs (e.g., miR-204-5p, miR-99a-5p, miR-21), proteins (e.g., glycolytic enzymes, HSP90), and lncRNAs (e.g., HOTAIR, DLEU1) have emerged as promising biomarkers for disease detection and monitoring. Exosomal cargo actively participates in HPV-related tumor progression. For example, miRNAs such as miR-21 and miR-146a modulate immune cell polarization and inflammatory signaling, while lncRNAs like HOTAIR promote oncogenic transcriptional programs. Exosomal proteins including HSP90 and ANXA1 facilitate extracellular matrix remodeling and immune evasion, thereby influencing tumor growth and metastasis. In HPV-positive head and neck and cervical cancers, exosomal cargo reflects HPV status, tumor progression, and treatment response. Therapeutic studies demonstrate the utility of exosomes in vaccine delivery, immune modulation, and drug delivery systems, including the use of PROTACs. However, clinical translation faces barriers including isolation protocol standardization, biomarker validation, and scalable production.
CONCLUSIONS: Exosomes hold great promise for integration into diagnostic and therapeutic workflows for HPV-related cancers. Future research should focus on resolving standardization issues, validating biomarkers in diverse cohorts, and optimizing engineered exosome platforms for targeted therapy.

Keywords: biomarkers; cervical cancer; exosomes; extracellular vesicles; head and neck squamous cell carcinoma (HNSCC); human papillomavirus (HPV); liquid biopsy

DOI: https://doi.org/10.3390/cancers17203386

Mol Clin Oncol. 2025 Dec;23(6): 104

Advances in exosomal non-coding RNAs in cervical cancer (Review).

Xingkui Xie, Hongwei Guan, Meng Li, Wei Gao, Kejia Wu.

Exosomes, extracellular vesicles (30-150 nm in diameter) released upon the fusion of multivesicular bodies with the plasma membrane, are pivotal mediators of intercellular communication through their cargo transport. The present review aimed to provide further insight into the molecular mechanisms by which exosomal non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs and circular RNAs, contribute to the development of cervical cancer (CC). There are currently no US Food and Drug Administration-approved exosome products for medical use. The present review highlights the critical role of exosomal ncRNAs in the pathogenesis of CC, including tumor initiation, progression, metastasis, angiogenesis and drug resistance, and discusses their potential as novel biomarkers for diagnosis, therapeutic targets and prognostic tools for CC. However, the long-term safety and efficacy of these ncRNAs requires further confirmation by clinical trials, which is essential before exosomes can be broadly adopted in CC. Although exosomes hold significant potential in the diagnosis, therapy and prognosis of CC, several challenges remain to be addressed before their translation into therapeutic use, including the standardization of exosome isolation and storage protocols, the optimization of drug-loading efficiency, precise control over cargo release kinetics and the completion of extensive clinical trials.

Keywords: biomarkers; cervical cancer; exosomes; non-coding RNAs; tumor microenvironment

DOI: https://doi.org/10.3892/mco.2025.2899

Adv Sci (Weinh). 2025 Oct 29. e11940

Red Blood Cell-Derived Exosomal miR-93-5p Promotes Lung Cancer Progression through PTEN Suppression.

Ning Li, Pushpa Dhilipkannah, Van K Holden, Ashutosh Sachdeva, Feng Jiang.

Red blood cells (RBCs), which are enucleated and mitochondria-deficient, have traditionally been considered essential for gas exchange and systemic metabolic regulation. Here, an unrecognized role for RBCs in promoting lung cancer progression is identified. In a cohort of 226 lung cancer patients and 239 healthy controls, significantly elevated levels of miR-93-5p are observed in RBCs and RBC-derived exosomes, but not in plasma, with higher levels correlating with advanced stage and poor prognosis. Functional assays demonstrate that RBC-derived exosomal miR-93-5p is transferred to tumor cells, where it suppresses PTEN and enhances proliferation, migration, and invasion. Conversely, exosomes released by lung cancer cells deliver miR-93-5p to RBCs, thereby augmenting its abundance within RBCs. Inhibition of miR-93-5p or restoration of PTEN abrogates these effects. In both subcutaneous and orthotopic mouse models, RBC-derived exosomal miR-93-5p accelerates tumor growth and reduces survival, whereas therapeutic delivery of antisense oligonucleotides targeting miR-93-5p suppresses tumor burden, reduces metastasis, and prolongs survival. Together, the novel function of RBCs as active participants in tumorigenesis is reported through exosomal transfer of oncogenic miR-93-5p, establishing a bidirectional tumor-RBC-tumor communication axis that promotes malignancy and offers new diagnostic and therapeutic opportunities in lung cancer.

Keywords: PTEN; exosomal miRNAs; lung cancer; red blood cells (RBCs); tumorigenesis

DOI: https://doi.org/10.1002/advs.202511940

Discov Oncol. 2025 Oct 31. 16(1): 1997

Harnessing the power of exosomes in leukemia: from molecular messengers to clinical applications.

Mohammad Amin Ansarian, Mahsa Fatahichegeni, Yuqi Wang, Juan Ren, Xiaoning Wang.

Exosomes, nanosized extracellular vesicles (30-150 nm), have emerged as pivotal mediators in leukemia pathogenesis, fundamentally altering our understanding of the disease and therapeutic approaches. These membrane-bound carriers transport complex molecular cargos, including proteins, nucleic acids, and lipids, facilitating intercellular communication that drives malignant transformation, treatment resistance, and remodeling of the bone marrow microenvironment. In leukemia, exosomes orchestrate angiogenesis, immune evasion, and disruption of normal hematopoiesis while serving as repositories of disease-specific biomarkers. Characteristic molecular signatures have been identified across various leukemia subtypes, including microRNA patterns (miR-155, miR-150 in CLL; miR-26a-5p in AML) and protein markers (IFITM3, CD146 in CML), which enable minimally invasive liquid biopsy-based diagnostics and real-time disease monitoring with high sensitivity and specificity. Therapeutically, exosomes function as natural drug delivery vehicles with inherent biocompatibility and barrier-crossing capabilities, while engineered platforms, including CAR-T cell-derived exosomes, offer novel immunotherapeutic strategies. Paradoxically, exosomes also mediate treatment resistance through intercellular transfer of resistant phenotypes, particularly in imatinib-resistant CML and chemoresistant AML, revealing both challenges and therapeutic targets. Clinical translation faces significant hurdles, including standardization of isolation protocols, optimization of cargo loading, scalable manufacturing, and regulatory framework development. The convergence of enhanced biological understanding, technological innovation, and evolving regulatory landscapes positions exosome-based strategies to revolutionize leukemia management through precision diagnostics and targeted therapies with reduced systemic toxicity.

Keywords: Biomarkers; Bone marrow microenvironment; Drug delivery; Exosomes; Extracellular vesicles; Immunotherapy; Leukemia; Liquid biopsy; Treatment resistance

DOI: https://doi.org/10.1007/s12672-025-03814-3