Treatment dependent impact of plasma-derived exosomes from head and neck cancer patients on the epithelial-to-mesenchymal transition

Abstract

BackgroundEpithelial to mesenchymal transition (EMT) is a key process in carcinogenesis of head and neck squamous cell carcinoma (HNSCC), contributing to tumor invasiveness, distant metastasis, and recurrence. Exosomes are known mediators and regulators of EMT. Here, we analyze the impact of exosomes that were primed by conventional therapy on EMT modulation.MethodsPlasmas of n = 22 HNSCC patients were collected before and after standard of care surgery and adjuvant or primary (chemo)radiotherapy. Exosomes were isolated by size exclusion chromatography. Upon co-incubation of exosomes with HNSCC cells, the cellular EMT profile was analyzed by flow cytometry and RT-qPCR. Wound healing assays were performed to evaluate migratory potential of exosome-treated cells.ResultsReduction of total exosome protein after therapy and in vitro exosome induced EMT profiles were dependent on the type of treatment. Exosomal TFG-β and miRNA cargo were partly responsible for observed exosome induced EMT changes. Exosomes from recurrent patients induced higher tumor cell migration after therapy than exosomes from disease-free patients.ConclusionsHNSCC patients’ exosomes from timepoints before and after therapy were able to confer therapy induced EMT modulation in vitro and have the potential to monitor the EMT process. Exosome induced changes in migratory potential emerged as discriminants of therapy outcome.

Tumor-Derived Exosomes and the Role of Liquid Biopsy in Human Papillomavirus Oropharyngeal Squamous Cell Carcinoma

“…Additional studies are essential, but identifying the changes in plasma TDEV proteomes, transcriptomes, and metabolomes before, during, and after therapy may accurately reflect cellular evolution in the primary TIME. These observations have significant translational implications for monitoring treatment response and disease recurrence 85 . Future applications of this approach have the potential to transform the care of patients with HPV + OPSCC.…”

“…Emerging insights into the mechanisms underlying TDEV reprogramming of the TIME will provide new opportunities to study selective TDEV-depleting strategies and interventional approaches in the clinical realm. A recent study evaluating whether conventional therapies influenced plasma TDEV cargo and function found that the cargo of TDEVs and their ability to induce an epithelial-to-mesenchymal transition was significantly enhanced after treatment 85,86 . Because the cargo carried by EVs has been involved in the modulation of tumor phenotypic transitions and progression, an exciting approach for the future is the possibility of targeting specific TDEV cargos with oncogenic properties to prevent progression and metastasis.…”

“…These observations have significant translational implications for monitoring treatment response and disease recurrence. 85 Future applications of this approach have the potential to transform the care of patients with HPV + OPSCC.…”

“…A recent study evaluating whether conventional therapies influenced plasma TDEV cargo and function found that the cargo of TDEVs and their ability to induce an epithelial-to-mesenchymal transition was significantly enhanced after treatment. 85,86 Because the cargo carried by EVs has been involved in the modulation of tumor phenotypic transitions and progression, an exciting approach for the future is the possibility of targeting specific TDEV cargos with oncogenic properties to prevent progression and metastasis. Another strategy might involve preventing the immunosuppressive effects of TDEVs, therapy overcoming tumor resistance to immunotherapies, or potentiating their effects.…”

Current trends in liquid biopsy and diagnostics—contributions from ASCO and ESMO 2022

“…Hofmann et al. haben kürzlich in einem Kollektiv von 22 Patienten gezeigt, dass Operationen und/oder Radiochemotherapie unterschiedliche Veränderungen der Tumorexosomen bedingen [ 7 ]. Die Induktion von epithelialer zu mesenchymaler Differenzierung bei Applikation von Tumorexosomen an Zellen ist ein mögliches Maß für das Tumoransprechen.…”