Prognostic Significance of Pretreatment Immune Cell Infiltration in MIBC After Definitive Chemoradiation

Analysis of muscle-invasive bladder cancer (MIBC) tumor samples from the NRG/RTOG 0524 and 0712 studies has helped shed light on the tumor immune microenvironment and identify prognostic immune biomarkers for chemoradiation therapy (CRT).

Results of this analysis were presented by Matthew Deek, MD, of Rutgers University, and colleagues at the American Society for Radiation Oncology 2023 Annual Meeting.

CRT is an organ-conserving treatment approach for locally advanced bladder cancer. There is belief that chemoradiation results in immunogenic stimulation, but further research is needed to confirm this effect. Bladder cancer is often a tumor with high immune cell infiltration.

Dr. Deek and colleagues studied tumor samples from NRG/RTOG 0524 and 0712—prospective clinical trials of CRT in MIBC—in an attempt to better profile the tumor immune microenvironment and identify prognostic immune biomarkers related to CRT. A total of 70 pretreatment tissue samples were profiled using Cofactor Genomics’ ImmunoPrism, an RNA sequencing assay that uses gene expression profiles to quantify immune cell populations in the tumor microenvironment.

Researchers estimated differential gene expression for different immune cell type proportions across all samples. They performed Kaplan-Meier survival analysis and log rank tests to evaluate differences in overall survival (OS), which were stratified by genes influenced by immune cell proportions or by genes associated with immune response signatures.

Among the immune cell proportions were CD8 T cells (median, 1.2%), CD4 T cells (median, 0.8%), Treg cells (median, 9.2%), CD19 B cells (median, 5.1%), M2 macrophages (median, 0.8%), and M1 macrophages (median, 0%).

Results of unbiased clustering based on gene expression profiles driven by immune cell proportions pointed to 2 groups: cluster 1 with a low percentage of immune cells and shorter OS (median, 31 months) and cluster 2 with a high percentage of immune cells and longer OS (median, 101 months).

Researchers also reported that higher expression of genes associated with T-cell infiltration (CD8A and ICOS) was associated with improved OS. A similar association was found for higher expression of IDO1, which is associated with the interferon gamma pathway.

“Increased immune cell proportions are prognostic for OS following CRT, as well as a higher expression of genes associated with T-cell infiltration interferon gamma signaling,” Dr. Deek and colleagues concluded, noting that these findings have implications for the integration of immunotherapy into MIBC management and should be further evaluated in the NRG/SWOG 1806 study.