IgG+ Extracellular Vesicles Measure Therapeutic Response in Advanced Pancreatic Cancer

Abstract

(1) 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) 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.

A Current Synopsis of the Emerging Role of Extracellular Vesicles and Micro-RNAs in Pancreatic Cancer: A Forward-Looking Plan for Diagnosis and Treatment

“…More particularly, IgG-positive EVs are reduced when there is a favorable response to treatment, whereas they are increased in case of tumor progression. This marker is considered beneficial for the identification of treatment responses in patients who do not express high levels of CA-19-9 [ 212 ].…”

The multifaceted roles of extracellular vesicles for therapeutic intervention with non-Hodgkin lymphoma

“…MRD was detected in 23% of ASC samples and associated with a worse PFS (13% vs. 53%) and OS (52% vs. 68%) [82] . As products of V(D)J rearrangements of immunoglobulin genes, Khodadoust et al "identified a total of 11 immunoglobulin derived neoantigens presented by MHC I from 4 of 7 FL/DLBCL tumors and both CLL samples" [83] . From EVs isolated with sucrose ultracentrifugation from plasma, flow cytometry results showed greater EV IgG+ expression in pancreatic ductal adenocarcinoma (PDAC) patients as compared to healthy controls [84] .…”

“…Additionally, lowering EV IgG+ levels post-treatment indicated a better response to chemotherapy for metastatic PDAC patients (AUC = 0.8311, P = 0.0020) [84] . Given their preservation of NHL phenotypes and roles in cell-to-cell communication, this aspect of EVs could also be utilized for monitoring the NHL disease and patient response to treatment [41,78,[81][82][83][84] . However, no studies to our knowledge have examined the presence of immunoglobulins on NHL EVs for MRD.…”