Extracellular Vesicle-Derived Protein File from Peripheral Blood Predicts Immune-Related Adverse Events in Gastric Cancer Patients Receiving Immunotherapy

Abstract

Immune checkpoint inhibitors (ICIs) initiate a new stage for gastric cancer (GC) therapeutics, and plenty of patients have already benefited from ICIs. Liquid biopsy promotes the development of precision medicine of GC. However, due to the lack of precision biomarkers of immune-related adverse events (irAEs), the safety of ICIs-treated GC patients cannot be guaranteed. In our study, GC patients treated with ICIs were included for investigating the correlation between irAEs of ICIs and corresponding outcomes. We also explored the potential of biomarkers of irAEs via EV-derived proteins. Dynamic plasma was taken from 102 ICIs-treated GC patients generated retrospectively or prospectively, who were divided into discovery and validating cohorts. Plasma EV-derived protein profiles were described, and two EV-proteins, inducible T-cell co-stimulator (EV-ICOS) and indoleamine 2,3-dioxygenase 1(EV-IDO1), from 42 vital proteins were screened to predict the prognosis of ICIs with irAEs. Our work is the first to propose that EV-proteins can predict ICIs-corresponding irAEs, which can be conducive to the diagnosis and treatment of GC patients, and to facilitate the screening of beneficiaries.

Exploratory analysis to predict pneumonitis during durvalumab consolidation therapy for patients with locally advanced non‐small cell lung cancer from proteomic profiling of circulating extracellular vesicles

“…For example, several studies have demonstrated that exosome‐derived PD‐L1 is a better indicator of disease and immune activity than plasma‐derived soluble PD‐L1. 35 , 36 Although only a limited number of studies have been conducted on using EV proteins to predict drug therapy‐induced AEs, 37 our research highlights the potential of EVs as biomarkers for predicting AEs.…”

“…For example, several studies have demonstrated that exosome-derived PD-L1 is a better indicator of disease and immune activity than plasmaderived soluble PD-L1. 35,36 Although only a limited number of studies have been conducted on using EV proteins to predict drug therapy-induced AEs, 37 our research highlights the potential of EVs as biomarkers for predicting AEs. NF-κB signaling, which is elevated before durvalumab treatment in patients with symptomatic pneumonitis, is a master regulator of inflammation in lung endothelial cells.…”

Efficacy and safety of immunotherapy combined with single-agent chemotherapy as second- or later-line therapy for metastatic non-small cell lung cancer

“…PBS with 5% glycerol and 10 μg/ml of biotinylated bovine serum albumin (BSA) were used as negative and positive controls, respectively. The EV expression array assay was performed by referring to previous studies ( 13 , 14 ). Briefly, the microarray slides were incubated with a 10 μl unpurified plasma sample diluted (1:10) in wash buffer (0.05% Tween20 in PBS) at room temperature for 2 h followed by overnight incubation at 4°C.…”

An updated review of gastrointestinal toxicity induced by PD-1 inhibitors: from mechanisms to management

“…Likewise, Jiang et al. noticed the occurrence of irAEs corresponds to a better disease control rate of immunotherapy in gastric cancer patients ( 86 ). Even, patients with multiple irAEs had a trend toward improved PFS and OS, as compared with patients with only a single irAE ( 82 ).…”