Related Experiment Video
Updated: Jul 2, 2025
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
A spatial proteomic study of platinum refractory HGSOC implicates dual AKT and WNT activity linked to an
Carly B Scalise1, Kaitlyn Kincaid1, Haley Thigpen2
1Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Alabama at Birmingham, Birmingham, AL, USA.
Objective:
Advanced-stage high-grade serous ovarian cancer (HGSOC) remains a deadly gynecologic malignancy with high rates of disease recurrence and limited, effective therapeutic options for patients. There is a significant need to better stratify HGSOC patients into platinum refractory (PRF) vs. sensitive (PS) cohorts at baseline to improve therapeutic responses and survival outcomes for PRF HGSOC.
Methods:
We performed NanoString for GeoMx Digital Spatial Profile (G-DSP) multiplex protein analysis on PRF and PS tissue microarrays (TMAs) to study the bidirectional communication of cancer cells with immune cells in the tumor microenvironment (TME) of HGSOC. We demonstrate robust stratification of PRF and PS tumors at baseline using multiplex spatial proteomic biomarkers with implications for tailoring subsequent therapy.
Results:
PS patients had elevated apoptotic and anti-tumor immune profiles, while PRF patients had dual AKT1 and WNT signaling with immunosuppressive profiles. We found that dual activity of AKT1 and WNT signaling supported the exclusion of immune cells, specifically tumor infiltrating lymphocytes (TILs), from the TME in PRF tumors, and this was not observed in PS tumors. The exclusion of immune cells from the TME of PRF tumors corresponded to abnormal endothelial cell structure in tumors with dual AKT1 and WNT signaling activity.
Conclusions:
We believe our findings provide improved understanding of tumor-immune crosstalk in HGSOC TME highlighting the importance of the relationship between AKT and WNT pathways, immune cell function, and platinum response in HGSOC.
Insights
Stratifying high-grade serous ovarian cancer (HGSOC) patients by platinum response is crucial. Spatial proteomic analysis revealed distinct immune and signaling profiles, differentiating platinum-refractory from platinum-sensitive tumors.
Area of Science:
- Oncology
- Immunology
- Proteomics
Background:
- Advanced-stage high-grade serous ovarian cancer (HGSOC) has poor outcomes and limited treatment options.
- Stratifying patients into platinum-refractory (PRF) versus platinum-sensitive (PS) groups is critical for improving therapy.
- Understanding tumor-immune interactions in the HGSOC tumor microenvironment (TME) is essential.
Purpose of the Study:
- To stratify HGSOC patients into PRF and PS cohorts using baseline biomarkers.
- To investigate the bidirectional communication between cancer cells and immune cells in the HGSOC TME.
- To identify proteomic biomarkers for tailoring HGSOC therapy.
Main Methods:
- Multiplex protein analysis using NanoString GeoMx Digital Spatial Profiling (G-DSP).
- Analysis of tissue microarrays (TMAs) from PRF and PS HGSOC tumors.
- Evaluation of cancer cell-immune cell communication within the TME.
Main Results:
- PS tumors showed elevated apoptotic and anti-tumor immune profiles.
- PRF tumors exhibited dual AKT1 and WNT signaling with immunosuppressive profiles.
- Dual AKT1/WNT signaling correlated with immune cell exclusion (e.g., tumor-infiltrating lymphocytes) and abnormal endothelial cells in PRF tumors.
Conclusions:
- Spatial proteomic biomarkers can effectively stratify PRF and PS HGSOC tumors.
- The interplay between AKT/WNT pathways, immune cell function, and platinum response is vital in HGSOC.
- Findings enhance understanding of tumor-immune crosstalk and inform therapeutic strategies for HGSOC.
More Related Videos
09:17Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma
Published on: September 13, 2022
09:40Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
