Plasma extracellular vesicle derived protein profile predicting and monitoring immunotherapeutic outcomes of gastric cancer

Abstract

Immune checkpoint inhibitor (ICI)‐based immunotherapy brought new hope for gastric cancer (GC) treatment. However, due to the lack of proper biomarkers, patient selection and outcome prediction for GC's immunotherapy remain unsatisfying. In this study, through applying an extracellular vesicle (EV) protein expression array, we assessed the correlation of plasma EV‐derived protein spectrum with outcomes of ICI‐related therapeutic combinations. Plasma from 112 GC patients received ICI‐related therapies were investigated retrospectively/prospectively as three cohorts. We identified four plasma EV‐derived proteins (ARG1/CD3/PD‐L1/PD‐L2) from 42 crucial candidate proteins and combined them as an EV‐score that robustly predicting immunotherapeutic outcomes at baseline and dynamically monitoring disease progression along with treatment. High EV‐score reflected microenvironmental features of stronger antitumour immunity, characterized by more activated CD8 + T/NK cells, higher TH1/TH2 ratio and higher expressions of IFN‐γ/perforin/granzymes in paired peripheral blood, which were verified by dataset analysis and in vivo experiments. EV‐score≥1 GC received more therapeutic benefits from ICIs, while EV‐score < 1 GC potentially benefited more from ICIs combining HER2‐targeted therapies. Collectively, through proposing a plasma EV‐score on protein level that powerfully predicting and monitoring GC's immunotherapeutic outcomes, our work facilitated clinical patient selection and decision‐makings, and provided mechanistical insights for immunotherapy‐related microenvironmental changes and improvements for current ICI‐regimens.

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

“…Compared to the patients without irAEs, patients diagnosed with grade ≥ 1 irAEs displayed comparable ORR (objective response rate) and better DCR (disease control rate) ( Figure S1A ). Furthermore, patients who developed grade ≥ 2 irAEs displayed slightly longer, yet statistically insignificant irPFS/irOS (immunotherapy-related progression-free survival/overall survival) than patients without irAEs or with grade ≥ 1 irAEs ( Figure S1B ) [ 17 ]. These basic features show that the occurrence of irAEs may correspond to a better disease control rate of immunotherapy in GC patients.…”

Visual analysis of global research on immunotherapy for gastric cancer: A literature mining from 2012 to 2022

“…Shen Lin was interested in individualized treatment of immunotherapy for GC, mainly explored the efficacy of immunotherapy in Epstein-Barr virus-associated GC, 38 multi-dimensional analyses of tumor immune microenvironment to predict the efficacy of immunotherapy in GC, 39 and plasma extracellular vesicle-derived protein profile to predict the immunotherapeutic outcomes of GC. 40 This suggests that screening suitable patients is one of the priorities of current research. Of course, authors from various countries, especially China and the United States, should strengthen cooperation to promote the development of this field.…”

From Conventional to Microfluidic: Progress in Extracellular Vesicle Separation and Individual Characterization

“…Many hundreds of different proteins, such as CD37, CD9, and CD63, have been discovered both in the vesicles and on the EV membrane and are necessary to maintain the normal operation of various life functions, they can also provide specific proteins that can be detected for early screening of disease. [ 63–67 ] The nucleic acids in EVs are composed of RNA and DNA. The amount of RNA in EVs is related to the cell origin, where cancer‐derived EVs generally contain more total RNA than EVs obtained from normal cells.…”