(UroToday.com) The 2024 IBCN annual meeting included a session on treatment response correlates, featuring a presentation by Dr. Trine Strandgaard discussing spatial proteomics and transcriptomics in patients unresponsive to BCG treatment. Patients with high-risk non-muscle invasive bladder cancer (NMIBC) are recommended treatment with BCG. The therapeutic effect of BCG is highly dependent on the host immune system and the tumor microenvironment. Previously, the cellular composition and the functional status of the tumor microenvironment have been shown to play crucial roles in BCG treatment efficacy:
From bulk to single cell analyses, understanding biomarkers is important given that characteristics of the tumor microenvironment are not available from bulk analyses. Moreover, there is increasing granularity given potential interactions, phenotypes, and mechanisms of resistance. Using spatial proteomics and transcriptomics, Dr. Strandgaard and colleagues investigated the immune cell landscape in a cohort of BCG-treated patients.
A total of 183 tumors from 111 patients with NMIBC treated with BCG were included on a tissue microarray, which included paired pre- and post-BCG tumors. They analyzed the tumor tissue using Imaging Mass Cytometry for simultaneous detection of 36 immune and tumor-related proteins. Ilastik was used to generate probability maps, and DeepCell Mesmer was used for cell segmentation. Markers were quantified for the mean intensity per cell. The GeoMx Digital Spatial Profiler was used for spatial proteomics and transcriptomics profiling of tumor and stromal areas.
After computing a neighborhood graph using the log normalized and z-scaled signal and embedding it using UMAP, Leiden clustering was performed on 360,673 cells to detect communities of unique cell types by interrogating the presence of phenotypic markers:
The investigators observed more macrophages (p = 0.02), CD4 T cells (p < 0.001), and CD8 T cells (p = 0.004) after BCG:
Similarly, they found enrichment of cellular neighborhoods composed of immune cells after treatment. Patients who progressed to muscle invasive bladder cancer after BCG had higher numbers of CD4 T cells (p = 0.034), CD8 T cells (p = 0.023), and NK cells (p < 0.001) prior to BCG. Additionally, Dr. Strandgaard found high pretreatment expression of interferon signaling pathways in tumor regions from patients with a signature of CD8 T cell exhaustion after BCG using GeoMx Digital Spatial Profiler transcriptomic analysis:
These data suggest that immune phenotypes are important for response. Dr. Strandgaard concluded her presentation discussing spatial proteomics and transcriptomics in patients unresponsive to BCG treatment with the following take-home points:
- The composition and functional status of the tumor microenvironment is associated with clinical and biological features such as immune cell abundance, CD8 T cell exhaustion, and progression
- A greater understanding of the tumor microenvironment may help identify patients unresponsive to BCG and improve the understanding of biological differences in tumor development and aggressiveness, ultimately improving patient outcomes
Presented by: Trine Strandgaard, MD, MS, PhD, Aarhus University, Aarhus, Denmark
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 International Bladder Cancer Network (IBCN) Annual Meeting, Bern, Switzerland, Thurs, Sept 19 – Sat, Sept 21, 2024