IgG+ Extracellular Vesicles Measure Therapeutic Response in Advanced Pancreatic Cancer

IgG+ 细胞外囊泡可衡量晚期胰腺癌的治疗反应

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作者:Nuno Couto, Julia Elzanowska, Joana Maia, Silvia Batista, Catarina Esteves Pereira, Hans Christian Beck, Ana Sofia Carvalho, Maria Carolina Strano Moraes, Carlos Carvalho, Manuela Oliveira, Rune Matthiesen, Bruno Costa-Silva

Background

Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second-leading cause of cancer deaths by 2030. Imaging techniques are the standard for monitoring the therapy response in PDAC, but these techniques have considerable limits, including delayed disease progression detection and difficulty in distinguishing benign from malignant lesions. Extracellular vesicle (EV) liquid biopsy is an emerging diagnosis modality. Nonetheless, the majority of research for EV-based diagnosis relies on point analyses of EVs at specified times, while longitudinal EV population studies before and during therapeutic interventions remain largely unexplored. (2)

Conclusions

We here propose that a population analysis of IgG+ EVs in PDAC plasma represents a novel method to supplement the monitoring of the PDAC treatment response.

Methods

We analyzed plasma EV protein composition at diagnosis and throughout PDAC therapy. (3)

Results

We found that IgG is linked with the diagnosis of PDAC and the patient's response to therapy, and that the IgG+ EV population increases with disease progression and reduces with treatment response. Importantly, this covers PDAC patients devoid of the standard PDAC seric marker CA19.9 expression. We also observed that IgG is bound to EVs via the tumor antigen MAGE B1, and that this is independent of the patient's inflammatory condition and IgG seric levels. (4) Conclusions: We here propose that a population analysis of IgG+ EVs in PDAC plasma represents a novel method to supplement the monitoring of the PDAC treatment response.

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