138P - Toward predicting immune checkpoint blockade response in oesophageal squamous cell carcinoma: Integrating tumour and blood characteristics

Background

Immune checkpoint blockade (ICB) holds promise for improving survival rates in oesophageal squamous cell carcinoma (ESCC). However, the lack of robust predictive biomarkers limits clinical outcome optimization. We hypothesized that analysing the spatial organization of tumours can offer insights into ICB response, potentially guiding the identification of reliable non-invasive predictive biomarkers in peripheral blood samples.

Methods

In the RAMONA trial (NCT03416244), tumour sections and peripheral blood samples were collected from 21 ESCC patients before their second-line treatment, either with nivolumab (anti-PD-1) alone or combined with ipilimumab (anti-CTLA4). Tumour sections were stained with the PhenoCycler platform using a 40-plex immunofluorescence panel to examine spatial tumour-immune interactions associated with clinical outcomes, including progression-free survival (PFS) and best overall response by RECIST version 1.1. Peripheral blood mononuclear cells (PBMCs) were isolated and profiled by 10x single-cell RNA-sequencing to compare cellular (sub)types between ICB responders and non-responders.

Results

Patients with prolonged PFS upon ICB (>8 months, n=3) exhibited more intratumoural aggregates of CD3+ T cells (including CD4+ and CD8+ populations), CD79a+ CD38+ B cells, and CD31/CD34+ endothelial cells, compared to patients with shorter PFS (<4 months, n=6; p<0.05). Conversely, tumours from the latter group showed more aggregates of MPO+ neutrophils, in close vicinity to CD4+ FOXP3+ regulatory T cells (p<0.05). These findings were consistent in pre-treatment peripheral blood samples. Specifically, T cells were more abundant in blood samples from patients who experienced prolonged PFS (n=6; p<0.05), while a higher abundance of myeloid cells was associated with shorter PFS (n=9; p<0.05). T cell subclustering revealed that predominantly effector CD8+ T cells and naïve CD4+ T cells correlated with prolonged PFS.

Conclusions

Our study suggests that integrating analyses of both tumour and peripheral blood characteristics can facilitate the discovery of robust non-invasive biomarkers for predicting ICB response.

Clinical trial identification

NCT03416244 (study completion: 2021-11-19).

Editorial acknowledgement

Legal entity responsible for the study

M. Ebert and D. Lambrechts.

Funding

Bristol Myers Squibb.

Disclosure

All authors have declared no conflicts of interest.