Integrating tumour and blood characteristics to predict responses to immune checkpoint inhibition in oesophageal squamous cell carcinoma

Previously, the phase II RAMONA study demonstrated the clinical benefit of immune checkpoint inhibition (ICI) in the second line treatment of older patients with advanced oesophageal squamous cell carcinoma (ESCC). In her research project, Dr Amelie Franken (VIB-KU Leuven Center for Cancer Biology, Leuven, Belgium) used data from this study to evaluate whether the spatial organization of tumours was associated with the chance for a response to ICI-based therapy.

Using single-cell and spatial profiling techniques, they were able to identify a correlation between the spatial organisation of the ESCC micro-environment and a clinical response to combined anti-PD-1 and anti-CTLA4 therapy. In fact, tumours from patients with stable disease or partial response upon treatment with an ICI exhibited higher intratumoral aggregates of CD3+ T-cells (CD4+ and CD8+), CD79a+ CD38+ B-cells, and CD31+/CD34+ endothelial cells compared to samples from patients with progressive disease. In contrast, samples of non-responders showed greater co-localisation of CD68+ MPO+ neutrophils and CD4+ FOXP3+ regulatory T-cells, suggesting a potential enhancement of immunosuppressive properties in these tumours. Interestingly, peripheral blood samples taken before the treatment reflected these findings, with a different expression of neutrophil markers between responders and non-responders. 

As such, these results underscore the potential of integrating tumour and blood analyses to identify robust non-invasive predictive biomarkers for ICB treatment.