bims-netuvo 2025-04-06 papers

In Vitro Model. 2025 Feb;4(1): 45-58

Pancreatic cancer extracellular vesicles stimulate Schwann cell activation and perineural invasion in vitro via IL-8/CCL2.

Emory Gregory, Isabel Powers, Azemat Jamshidi-Parsian, Robert J Griffin, Younghye Song.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related deaths, and perineural invasion (PNI), in which cancer cells infiltrate nerves, enables metastasis in most patients. PNI is largely attributed to Schwann cells (SC) that, when activated, accelerate cancer cell migration towards nerves. However, this cancer-associated reprogramming is generally under-appreciated. Additionally, tumor extracellular vesicle (EV) facilitation of cancer aggravation is well documented, but more investigation is required to better understand their role in PNI. Here, we assessed whether PDAC EVs mediate PNI via SC activation using tissue-engineered in vitro platforms and PANC-1 and HPNE human cell lines as models.
Methods: NanoSight, Luminex®, and proteomic-pathway analyses characterized tumor (PANC-1) and healthy cell (HPNE) EVs. Human Schwann-like cells (sNF96.2) were embedded in decellularized nerve matrix hydrogels and then treated with EVs and a cargo-function-blocking antibody. Immunofluorescence and Luminex® multiplex assays assessed Schwann cell activation. Subsequently, sNF96.2 cells were co-cultured with EVs and either PANC-1 or HPNE cells; Transwell® invasion assays with SC-conditioned media were also conducted to establish a mechanism of in vitro PNI.
Results: PANC-1 EVs contained higher levels of interleukin-8 (IL-8) signaling-associated proteins than HPNE EVs. Within nerve-mimetic in vitro testbeds, PANC-1 EVs promoted sNF96.2 activation per cytoskeletal marker alterations and secretion of pro-tumorigenic cytokines, e.g., chemokine ligand-2 (CCL2), via IL-8 cargoes. Furthermore, the IL-8/CCL2 axis heightened PANC-1 invasiveness.
Conclusion: These findings highlight the potential role of PDAC EVs in PNI, which necessitates continued preclinical assessments with increased biodiversity to determine the efficacy of targeting IL-8/CCL2 for PNI.
Supplementary Information: The online version contains supplementary material available at 10.1007/s44164-025-00083-w.

Keywords: Extracellular vesicles; Glia; Pancreatic cancer; Perineural invasion; Tissue engineering

DOI: https://doi.org/10.1007/s44164-025-00083-w

Radiol Med. 2025 Apr 01.

A comprehensive study on the radiomic score derived from perineural invasion in gastric cancer and its correlation with the overall survival of patients.

Yueling Wang, Xuhui Fan, Zai Luo, Qingguo Wang, Yuan Fang, Chao Han, Zhengjun Qiu, Han Wang, Chen Huang.

BACKGROUND: Perineural invasion (PNI) is closely related to the prognosis of gastric cancer (GC) patients. However, a noninvasive tool for accurately and reliably predicting the PNI is lacking.
METHODS: The clinical and imaging data of 278 patients from institution I and 39 patients from institution II were retrospectively analyzed. Radiomic features were extracted from the intratumoral and peritumoral regions. Seven independent machine learning (ML) algorithms are used to develop the models. Kaplan-Meier survival analysis and Cox proportional hazards analysis were carried out to compare 3-year and 5-year overall survival (OS) differences among various subgroups based on PNI and radiomic scores.
RESULTS: T stage and lymphovascular invasion (LVI) were significantly correlated with the PNI (P < 0.01). The OS of patients with different PNI status was significantly different (P < 0.05). Gradient boosting tree is the best ML algorithm. The area-under-the-curve (AUC) values of the optimal radiomics model in the internal test set and external test set were 0.901 and 0.886, respectively. After the introduction of clinical variables T stage and LVI, the performance of the model further improved in predicting the PNI of GC patients, with the AUC of 0.904 in the internal test set and 0.886 in the external test set. The difference in 3-year OS (P = 0.005) and 5-year OS (P = 0.015) among patients with varying radiomic scores was statistically significant.
CONCLUSION: Radiomics combined with intratumoral and peritumoral features is feasible for evaluating the PNI of GC patients. The prognosis of patients with different radiomic scores was statistically significant.

Keywords: Computed tomography; Gastric cancer; Perineural invasion; Radiomics

DOI: https://doi.org/10.1007/s11547-025-01993-1

Biochem Biophys Res Commun. 2025 Mar 28. pii: S0006-291X(25)00401-2. [Epub ahead of print]761 151687

Nerve infiltration of bladder cancer predicts response to immunotherapy.

Xinyi Lu, Kun-Ming Shui, Hao Ji, Jia-Yu Chen, Chao Yan, Pengchao Li, Tao Xu.

Immune checkpoint therapy (ICT), particularly Programmed Death-1 (PD1) antibody treatment, has revolutionized the clinical management of many previously undruggable types bladder cancer (BC). However, it remains unclear whether nerve-invaded BC patients benefit from immunotherapy. Here, we utilized public databases to show that BC patients with high neural signal expression are associated with more advanced tumor stages. Analysis of patient tumor samples revealed significant neural expression within classical tertiary lymphoid structures, and this was inversely correlated with the immune levels. In a denervated mouse bladder tumor model, we found that nerve ablation significantly inhibited tumor progression. Single-nucleus RNA sequencing data revealed that nerve fibers suppressed the activity of immune cells within the tumor microenvironment, while denervation alleviated immune suppression and restored cytotoxic activity. Denervation enhanced the immune response by downregulating Pdcd1 (encoded Pd1) expression in natural killer (NK) cells. Pathological analysis of patient tumor samples further confirmed that higher neural abundance was strongly correlated with PD1 expression. Finally, through database analysis and clinical sample validation, we demonstrated that BC patients with high neural signaling showed better responses to ICT. Overall, this study highlights the potential for targeted immunotherapy in nerve-invasive BC, providing a novel framework for enhancing the effectiveness of ICT in treating this subset of bladder cancer.

DOI: https://doi.org/10.1016/j.bbrc.2025.151687