Abstract 3411
Background
Gastrointestinal stromal tumours (GISTs) account for 1% of all primary gastrointestinal cancers. In cancer, suppressive immune checkpoints, including butyrophilin sub-family 3A/CD277 receptors (BTN3A), programmed death protein (PD-1) and its ligand PD-L1, are often hyper-activated to ensure an effective evasion of tumor cells from immune surveillance. Since recent studies showed that PD-1 and PD-L1 expression in cancer may be an important prognostic factor, the aim of our study was to investigate if soluble forms of inhibitory immune checkpoints can help predict survival in metastatic GIST patients.
Methods
Using specific homemade ELISA assays not yet commercially available, the plasma PD-1, PD-L1, BTN3A1 and pan-BTN3As levels were analyzed in 20 metastatic GIST patients harbouring c-KIT exon 11 mutations, before starting treatment with 400 mg Imatinib. Survival curves were estimated by using the Kaplan-Meier method and log-rank test to evaluate significant differences among them. Data was generated using the MedCalc software for Windows, version 18.2.1.
Results
Kaplan-Meier survival analysis was used to characterize prognostic relevance of soluble PD-1, PD-L1, BTN3A1 and pan-BTN3As in metastatic GIST patients, suggesting that their plasma levels could serve as survival predictor. For each analyzed biomarker, statistically significant differences in progression free-survival (PFS) between patients with plasma concentrations above and under median values were detected. Plasma level thresholds correlated with shorter survival and poor prognosis were established for PD-1 (>6.89 ng/ml), PD-L1 (>0.74 ng/ml), BTN3A1 (>7.19 ng/ml) and pan-BTN3As (>4.38 ng/ml). Conversely, patients with plasma levels under thresholds showed a median PFS that was approximately 58 months longer than to the previous.
Conclusions
Our study, for the first time, reveals that monitoring the concentration of soluble forms of inhibitory immune checkpoints in plasma can help predict survival in metastatic GIST patients and therefore improve their treatments. We showed that high plasma levels of these immune checkpoints correlate with poor outcome and could be used in future as prognostic factors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1735 - mTOR inhibition in the treatment of resistant breast cancer
Presenter: María Rodriguez
Session: Poster Display session 1
Resources:
Abstract
6068 - Study of Photodynamic therapy in vitro
Presenter: Irene Jiménez Munguía
Session: Poster Display session 1
Resources:
Abstract
3011 - The potential of neratinib plus dasatinib in overcoming and preventing neratinib resistance in HER2-positive breast cancer models
Presenter: Neil Conlon
Session: Poster Display session 1
Resources:
Abstract
2644 - Novel HDACi, MHY446, induces apoptosis via regulation of mitochondria-endoplasmic reticulum interaction in HCT116 human colorectal cancer cells
Presenter: Nam Deuk Kim
Session: Poster Display session 1
Resources:
Abstract
3085 - Dual inhibition of TGF-β and AXL as a novel treatment for colorectal cancer
Presenter: Davide Ciardiello
Session: Poster Display session 1
Resources:
Abstract
1314 - PARP inhibition enhances cisplatin sensitivity in cervical cancer by modulating β-catenin signaling
Presenter: Minakshi Mann
Session: Poster Display session 1
Resources:
Abstract
2417 - Synergistic effect of DSF combined treatment with cisplatin in atypical teratoid/rhabdoid tumors (AT/RT)
Presenter: Seung Ah Choi
Session: Poster Display session 1
Resources:
Abstract
1149 - Reactive oxygen species induced by OSU-A9 inhibit the growth of duodenal cancer and gastric cancer cells through dephosphorylating intranuclear pyruvate kinase muscle isozyme M2
Presenter: Li-Yuan Bai
Session: Poster Display session 1
Resources:
Abstract
1862 - New therapy for intrahepatic cholangiocarcinoma targeted to cancer associated fibroblasts
Presenter: Takahiro Yamanaka
Session: Poster Display session 1
Resources:
Abstract
782 - Macrophage-cancer cell fusion is mediated by Phosphatidylserine-CD36 receptor interaction and induced by ionizing radiation
Presenter: Ivan Shabo
Session: Poster Display session 1
Resources:
Abstract