Immunological and Viral Profiles of Squamous Cell Carcinoma in Transplant and Non-Transplant Patients in Singapore
- Oh, Choon Chiat
- Lim, Boon Yee
- Lee, Elizabeth Chun Yong
- Kannan, Bavani
- Tang, Po Yin
- Ko, Tun Kiat
- Koh, Clara Wei Teng
- Chan, Kuan Rong
- Chan, Jason Yongsheng
Background
Cutaneous squamous cell carcinoma (cSCC) remains poorly understood at the molecular level, both in the immunocompetent and immunosuppressed population with skin of colour. Data on the diversity of viruses found in cSCC is also lacking.
Objectives
We aimed to characterise the immunological and molecular profiles of cSCC in organ transplant recipients (OTR) and non-transplant recipients in an Asian cohort (n = 53) and explore the diversity of viruses detected.
Methods
Gene expression analysis was performed on snap-frozen cSCC tissues using the NanoString PanCancer IO360 panel. Viral detection was performed using the Twist Comprehensive Viral Research Panel.
Results
cSCC presented dysregulation of immune response pathways and tumour microenvironment remodelling compared to adjacent normal skin tissue. Cell-type profiling based on gene expression profiles showed higher levels of exhausted CD8 cells, neutrophils, and cytotoxic cells in tumour cells. Furthermore, three distinct clusters of cSCC gene signatures could be observed, where Cluster 3 with the highest Tumour inflammation signature (TIS) scores displayed distinct upregulation of most pathways suggesting a more inflamed or “hot” tumour phenotype. cSCC of OTR exhibited greater expression of tumour markers (AQP9, SERPINA1) and reduced expression of T-cell cytokines (CXCL10, CXCL11). Viruses were particularly enriched in tumour tissue, as compared with normal skin. In addition, there was an enrichment of detectable viruses in transplant-associated cSCC, with several tumours harbouring multiple viruses (HPV, EBV, MCV, and TTV).
Conclusions
cSCC is marked by a pro-tumorigenic immune environment with altered immune cell populations. These findings support the potential for stratified, immune-tailored treatment approaches for cSCC, especially in OTR who have a higher disease burden. Future studies on the possible oncogenic role of the detected viruses can be undertaken.