1144P - High-plex spatial profiling of cutaneous squamous cell carcinoma to identify biomarkers associated with clinical outcomes: The cMIC study

Background

Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer. Early stage cSCC is often cured with simple resection +/- radiotherapy, though some can recur, most commonly in immunosuppressed (IS) individuals. In advanced cSCC, approximately 50% of patients develop primary resistance to immune checkpoint inhibitors (ICI). There is a need to identify biomarkers by characterising the tumour microenvironment (TME) within different clinical groups.

Methods

Our retrospective study profiled whole tissue sections from n=50 patients from the Princess Alexandra Hospital. Study groups (G) included immunocompetent patients with (G1) de novo, localised cSCC (n=10), (G2) regional nodal metastasis (n=10), (G3) locoregional recurrent disease (n=10), (G4) recurrent/metastatic disease treated with ICI (n=10) and (G5) IS patients (n=10). In this exploratory study, we designed a high-dimensional Nanostring GeoMx Digital Spatial Profiling (DSP) experiment which enabled simultaneous readout of >80-plex proteins in the TME to profile immune cell content, immuno-oncology drug targets, cell lineage and architecture. These features within the TME were measured against the clinical groupings to identify differentially expressed proteins between the groups for future biomarker analysis.

Results

Our preliminary analysis has identified distinct cell phenotype compositions within the TME associated with the clinical groupings. Within the tumour there was a reduction in expression of VISTA and STING immune signaling markers in localized disease (G1/2 vs G4). This was most notable within the stomal compartments. G3/4 had a lower expression of IDO1/STING/VISTA immune signaling markers compared with G5 IS individuals. Moreover, we identified an increased metabolic activity in patients with resistant disease.

Conclusions

Our study highlights the utility of spatial proteomic profiling of the TME in cSCC for the identification of biomarkers associated with biologically distinct clinical groups. This study provides the foundation work for prospective validation of putative biomarkers associated with therapy response and resistance.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Metro South Hospital and Health Services.

Funding

Princess Alexandra Research Foundation.

Disclosure

R. Ladwa, S. Porceddu: Financial Interests, Personal, Advisory Board: MSD, Sanofi. All other authors have declared no conflicts of interest.