bims-exocan 2026-07-19 papers

Issue of 2026–07–19
five papers selected by
Muhammad Rizwan, COMSATS University

Int J Gen Med. 2026 ;19 602593

Exosome-Mediated Macrophage Polarization in Gastric Cancer: Inflammatory and Neuroinflammatory Mechanisms and Therapeutic Potential.

Wei An, Ze Jin, Yan Li.

Gastric cancer progression is driven by intricate crosstalk among exosomes, macrophage polarization, inflammatory dysregulation, and tumor-associated neuroinflammation within the tumor microenvironment, which collectively form a reciprocal vicious cycle. As critical intercellular mediators, exosomes derived from tumor cells, immune cells, and stem cells deliver microRNA cargos to orchestrate M1/M2 macrophage balance and modulate neuroinflammatory states, exerting either pro-tumor or anti-tumor effects. M1 macrophage-derived exosomal miRNAs suppress PD-L1 and NLRP3 signaling, reduce pro-inflammatory cytokine release, ameliorate neuroinflammation, and enhance anti-tumor immunity. Conversely, tumor cell- and M2 macrophage-derived exosomes drive M2 polarization via the MAPK/ERK and PI3K/Akt pathways, amplifying the secretion of immunosuppressive cytokines and exacerbating neuroinflammatory progression. Stem cell- and traditional Chinese medicine-derived exosomes reverse immunosuppression by targeting the STAT3 pathway, polarize macrophages toward the M1 phenotype, and attenuate tumor-associated neuroinflammation. These regulatory events converge on the NF-κB and NLRP3 inflammasome pathways to shape the inflammatory and neuroinflammatory microenvironment. Preclinical evidence confirms that exosome-based interventions reduce tumor burden by remodeling macrophage phenotypes, restoring inflammatory homeostasis, and ameliorating neuroinflammation. This review identifies exosomal regulators as promising targets for rebalancing macrophage polarization, inflammation, and neuroinflammation, providing a framework for advancing gastric cancer therapeutics.

Keywords: exosome; gastric cancer; inflammation; macrophage polarization; miRNA; tumor microenvironment

DOI: https://doi.org/10.2147/IJGM.S602593

Transl Cancer Res. 2026 Jun 30. 15(6): 502

Exosome-mediated regulation of the immune microenvironment via JAK/STAT signaling promotes pancreatic cancer progression.

Shunxin Hao, Zhi Yao, Can Li, Tao Xiong, Jingxi Song, Yifeng Liu.

Background: Pancreatic cancer is characterized by a profoundly immunosuppressive microenvironment. This study aimed to investigate whether pancreatic cancer-derived exosomes contribute to tumor progression and CD8+ T-cell dysfunction in relation to Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling.
Methods: Exosomes derived from PANC-1 cells were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. Their effects on cell proliferation, migration, invasion, and JAK/STAT signaling in PANC-1 cells were evaluated. CD8+ T cells isolated from commercially obtained peripheral blood mononuclear cells (PBMCs) were co-cultured with exosome-treated PANC-1 cells to assess T-cell exhaustion, cytokine secretion, and proliferative function.
Results: Exosome treatment enhanced PANC-1 cell proliferation, migration, and invasion, accompanied by increased phosphorylation of JAK1/STAT3. CD8+ T cells co-cultured with exosome-treated PANC-1 cells exhibited increased expression of programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), reduced tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) secretion, and impaired proliferative capacity. These effects were partially attenuated by JAK/STAT inhibition.
Conclusions: Pancreatic cancer-derived exosomes are associated with tumor progression and CD8+ T-cell dysfunction in a co-culture model, potentially involving JAK/STAT signaling. These findings suggest that the exosome-JAK/STAT axis may represent a potential target for therapeutic intervention, pending further validation.

Keywords: CD8+ T cell exhaustion; Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT pathway); Pancreatic cancer; exosomes; tumor microenvironment (TME)

DOI: https://doi.org/10.21037/tcr-2025-1-2903

Int J Mol Sci. 2026 Jul 03. pii: 5976. [Epub ahead of print]27(13):

The Multifaceted Role of Extracellular Vesicles in Triple Negative Breast Cancer.

Serena El Rayes, Ebaa Ababneh, Varun Nannuri, Manjusha Vaidya, Kiminobu Sugaya, Jihe Zhao.

Triple negative breast cancer (TNBC) is an aggressive and heterogeneous subtype of breast cancer characterized by the absence of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), resulting in limited options for targeted therapy and high rates of metastasis, recurrence and death. Extracellular vesicles (EVs) have emerged as central mediators of TNBC pathophysiology, functioning as key intercellular communication vehicles transporting oncogenic proteins, nucleic acids, lipids, and metabolites. These EV-mediated interactions promote tumor microenvironment (TME) remodeling, immune evasion, metastatic niche formation, and therapeutic resistance. Given their stability, accessibility, and molecular complexity, EVs also represent promising diagnostic and prognostic biomarkers for TNBC. Advances in isolation and molecular profiling technologies have enabled the identification of EV-associated signatures that predict therapeutic response and stratify patient risk. Beyond their utility as biomarkers, EVs are rapidly emerging as therapeutic targets and delivery platforms, demonstrating efficacy in transporting chemotherapeutics, RNA-based therapeutics, immune modulators, and photosensitizers with enhanced targeting specificity and therapeutic efficiency. Collectively, EVs play a multifaceted role in TNBC biology, serving simultaneously as drivers of disease progression, minimally invasive biomarkers, and versatile therapeutic vehicles. The integration of EV-centered diagnostics, multi-omic profiling, and engineered therapeutics holds significant potential to transform TNBC management and advance precision oncology for this challenging breast cancer subtype.

Keywords: extracellular vesicle; triple negative breast cancer

DOI: https://doi.org/10.3390/ijms27135976

Extracell Vesicles Circ Nucl Acids. 2026 ;7(2): 675-699

Research on exosomes in cancer multidrug resistance and clinical translation.

Wenxin Zhang, Mengyuan He, Xiaoli Cheng, Qingqing Chai, Aixue Li, Fengna Li, Yongwei Gu, Kang Fang, Rong Rong, Jiyong Liu.

Multidrug resistance (MDR) is a major clinical challenge that limits the efficacy of multiple cancer treatment modalities, including chemotherapy, targeted therapy, immunotherapy, monoclonal antibody therapy, and antibody-drug conjugates. In recent years, exosomes (Exos), nanoscale vesicles involved in intercellular communication, have attracted increasing attention for their roles in the formation and spread of MDR. A growing body of evidence suggests that Exos mediate the transfer of resistance-related molecular signals among drug-resistant cancer cells, drug-sensitive cancer cells, and stromal cells, such as cancer-associated fibroblasts and tumor-associated macrophages, through the selective packaging of noncoding RNAs, functional proteins, and metabolic regulators. These molecular signals may induce the reprogramming of signaling pathways, metabolism, and epigenetic states in recipient cells, thereby promoting the acquisition of cancer stem cell-like properties and a drug-resistant phenotype. In turn, these changes may contribute to the establishment of a drug resistance-supporting tumor microenvironment. This review systematically summarizes the molecular mechanisms by which Exos contribute to multidrug resistance, with a particular focus on their roles in cargo sorting, microenvironmental crosstalk, and the functional reprogramming of recipient cells. It also discusses their potential for clinical translation in resistance monitoring and reversal therapy. In addition, this review further discusses the key challenges currently facing the field and provides perspectives on future research directions.

Keywords: Exosomes; multidrug resistance; therapy resistance; tumor microenvironment

DOI: https://doi.org/10.20517/evcna.2025.191

Int J Nanomedicine. 2026 ;21 576489

Bioengineered Exosome-Magnetic Nanoplatform for Precision Therapy of Hepatocellular Carcinoma via Dual-Targeted Drug Delivery.

Yongsheng Han, Shixian Yan, Ruohan Wan, Xingjing Li, Guanlin Wu.

Introduction: Hepatocellular carcinoma (HCC) continues to pose a significant threat to global health, contributing substantially to worldwide cancer-related mortality, particularly in high-incidence regions such as Asia, where current treatment strategies are often limited by poor drug delivery efficiency, systemic toxicity, and drug resistance.
Methods: To address these critical challenges, we developed an innovative dual-targeted nanoplatform (Exo-SPIONs-SRF/CGA) that synergistically combines the natural tumour-homing capability of HCC-derived exosomes with the magnetic guidance of superparamagnetic iron oxide nanoparticles (SPIONs) for precision drug targeting. This nanoplatform co-encapsulates SRF and CGA to improve the therapeutic index by enhancing desired responses and minimizing undesired side effects.
Results: The exosome component provides inherent biological targeting to HCC cells. At the same time, the incorporated SPIONs enable external magnetic field-guided spatial control, collectively ensuring superior tumour accumulation compared to conventional delivery systems. Furthermore, the platform's tumour microenvironment-responsive release characteristics ensure localized drug activation, maximizing the therapeutic index through spatial and temporal control of drug availability. In vitro and in vivo evaluations demonstrated that this nanoplatform significantly enhances tumour suppression and drug retention while reducing systemic side effects compared to monotherapies or single-modality nanocarriers.
Discussion: The Exo-SPIONs-SRF/CGA platform represents a promising strategy in HCC treatment, addressing fundamental limitations of current therapies by simultaneously overcoming biological barriers to drug delivery, enhancing therapeutic efficacy through synergistic drug combinations, and minimizing collateral damage to healthy tissues, thereby advancing the frontier of precision oncology toward more effective and safer HCC management.

Keywords: drug delivery; dual targeting; exosome; hepatocellular carcinoma; precise treatment

DOI: https://doi.org/10.2147/IJN.S576489