Abstract 38P
Background
Regulatory T cells (Treg) play a crucial role as prognostic factors and intervention targets for isocitrate dehydrogenase (IDH)-wild type (wt) glioblastoma (GBM). The study aimed to construct a model predicting the Treg infiltration in IDH-wt GBM patients using pathomics techniques and explore related biological processes.
Methods
Flow cytometry was used to detect the proportion of Treg in orthotopic mouse glioblastoma brain tissue. Clinical data of IDH-wt GBM patients from the TCGA database were analyzed retrospectively. Features were extracted from HE-stained biopsy sections using the Pyradiomics package. The pathomics model was constructed using the Gradient Boosting Machine algorithm after performing feature selection with mRMR and Relief algorithms. Cox proportional hazard regression analysis was employed to access the association between pathomics score (PS) and overall survival (OS). Transcriptomic data were analyzed through GSEA set enrichment, differential gene expression, and correlation analyses.
Results
The study established a pathomics model with 3 pathomics features that effectively predicted Treg infiltration (Training set: AUC=0.807; Validation set: AUC=0.735). PS positively correlated with high Treg expression. Survival analysis indicated that patients with high PS had significantly lower OS than the low PS group (median survival time: 12.0 vs 14.4 months; p=0.009). Multivariate COX analysis revealed that high PS expression independently served as a prognostic risk factor for IDH-wt GBM patients (HR, 2.16; 95% CI, 1.269-3.677; p=0.005). Subgroup analysis showed that high PS was a risk factor for OS in patients receiving chemotherapy (HR, 2.232; 95% CI, 1.309-3.905; p=0.003) or radiotherapy (HR, 1.882; 95% CI, 1.161-3.049; p=0.01).GSEA enrichment analysis revealed significant associations of PS with the NOTCH, IL-6/JAK/STAT3 signaling pathways. High PS significantly correlated with elevated RAD50 expression.
Conclusions
The developed pathomics model, based on machine learning algorithms, can noninvasively predict Treg infiltration and prognosis in IDH-wt GBM patients. The biological processes related to the model may involve RAD50 and pathways, including NOTCH, IL-6/JAK/STAT3.
Legal entity responsible for the study
The authors.
Funding
The Joint Funds for the Innovation of Science and Technology, Fujian Province (No.2021Y9301).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
137P - First-in-human results from a Phase I dose-escalation study of VSV-GP (BI 1831169) in patients with advanced solid tumors
Presenter: Stephane Champiat
Session: Poster Display
138P - Generation of frameshift mutated TGF_R2-specific T cells in healthy subjects following administration with cancer vaccine candidate FMPV-1/GM-CSF
Presenter: Else Inderberg
Session: Poster Display
139P - Safety and clinical activity of a novel anti-CCR8 antibody (LM-108) as a single agent or in combination with pembrolizumab in patients with advanced solid tumors: Results of phase 1 study
Presenter: Alexander Starodub
Session: Poster Display
140P - Eliciting mAbs targeting MHC-bound peptides with a novel antibody discovery platform
Presenter: Elli Sandberg
Session: Poster Display
141P - An IgE antibody targeting the melanoma-associated Chondroitin Sulfate Proteoglycan 4
Presenter: Lais Cristina Palhares
Session: Poster Display
142P - Identifying novel immunotherapy targets using machine learning and ex vivo validation
Presenter: Marcellus Augustine
Session: Poster Display
143P - Advancing Cancer Immunotherapy via HLA-G Pathway Modulation with UCB4594
Presenter: Ann WHITE
Session: Poster Display
144P - Discovery of CBO421, a first-in-class Drug Fc-Conjugate (DFC), targeting CD73 in Cancer
Presenter: Simon Döhrmann
Session: Poster Display
145P - An Engineered Ligand-Trap Biologic Targeting the CD47 Signaling Pathway for Cancer Treatment with Superb Efficacy and Safety Profiles
Presenter: ZONG SEAN JUO
Session: Poster Display
146P - A Novel Allosteric Oral Immunotherapy Small Molecule Modulates Adenosine 2A Receptor Signaling and Restores Anti-Tumor Immune Responses
Presenter: David Pejoski
Session: Poster Display