Abstract 760P
Background
Cutaneous squamous cell carcinoma (cSCC) is a prevalent skin cancer and poses a significant health burden globally, especially among immunocompromised individuals. This study aims to profile cSCC in Organ Transplant Recipients (OTR) and Non-Transplant Recipients (NTR) in an Asian cohort in Singapore.
Methods
Bulk RNA expression analysis was performed on 44 snap-frozen cSCC tissue samples, profiling 770 genes using the nCounter PanCancer IO 360 Panel. Analysis included 7 matched pairs of normal skin and cSCC samples, and a comparison between OTR (n = 6) and NTR (n = 7) cSCC groups using nSolver software.
Results
Cluster analysis classified normal skin and cSCC into two distinct groups. cSCC exhibited upregulated immune response pathways (cytokine, chemokine, and interferon signalling), tumor microenvironment remodelling (matrix remodelling, metastasis, myeloid compartment), intracellular signalling (PI3K-Akt, MAPK), cell proliferation and metabolic stress pathways. Cell type profiling revealed increased neutrophils, cytotoxic cells, and macrophages and decreased mast cells in cSCC (p < 0.001). Unsupervised clustering of all cSCC samples revealed 3 groups with distinct pathway scores. Cluster 1 showed a downregulation of immune-oncologic pathways, Cluster 2 displayed diverse patterns of pathway expression, and Cluster 3 showed a widespread upregulation. Tumor Inflammation Signature (TIS) scores were highest in Cluster 3 compared to Clusters 2 and 1 (7.54 vs. 6.71 vs. 5.75, respectively; p < 0.001), suggesting an inflamed or “hot” tumor phenotype. Comparative analysis of OTR cSCC samples revealed increased CD45+ cells and neutrophils, and decreased T-cells (p < 0.001) compared.to NTR samples. Pathway analysis highlighted increased immune-oncologic signalling, with topmost upregulation of myeloid compartment activity in the OTR group.
Conclusions
Distinct gene expression pathways and immune subgroups were identified in cSCC, along with varied immunophenotypic and molecular signatures between OTR and NTR. These findings suggest the potential for stratified treatment based on specific immune profiles in cSCC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.