A.L. Ferguson*1,2,3, A.R. Sharman1,3, C. Zilberg 4,14,15, R.O. Allen1,3,15, T. Ye8, E. Willie8, J.H. Lee10, H. Low4,7; S. Ch’ng4,7,9, C.E. Palme7, B. Ashford11,12, M. Ranson11,13, J.R. Clark4,7,9, E. Patrick6,8, D.L. Damian 4,14,15, R. Gupta #,4,5, U. Palendira #,1,2,3,15.
Cutaneous Squamous Cell Carcinoma (cSCC), has a mortality rate that is 8th among all cancers. Most cSCC can be treated with surgery with good local control. However, a subset of tumours that are large, infiltrate the subcutaneous tissue, demonstrate poor differentiation or perineural invasion (PNI) are considered at high-risk of local recurrence or developing metastases. Immunosuppressed patients, such as organ transplant recipients are at significantly higher risk of developing recurrent and metastatic cSCC suggesting that the immune system plays a critical role in progression and control of cSCC.
High-dimensional Imaging mass cytometry (IMC) was utilised to examine the TME of primary and metastatic cSCC tumours. Tumour specimens taken from cSCC patients were separated into primary tumours that never progressed (NP), Primary tumours that had disease progression (DP) including patients absent of clinical immune-suppression (ACIS) with both primary (P) and metastatic (Met) lesions and tumours of DP immunosuppressed patients (P, Met).
We found significant differences in the T cell and leukocyte immune composition of primary tumours that never progressed compared to primary tumours from DP patients ACIS. We also found significant spatial differences in primary tumours from these patients including cell-interactions and specific regions present in the TME landscape. Regional analysis of the TME showed squamous cell-enriched tumour regions associated with diseases-progression. Interestingly, we also show active expansion of B cells in metastatic tissue indicating a possible regulatory role of these B cells and a potential novel immunotherapy target.
Our findings indicate that the early events that shape the immune responses in primary tumours dictate progression and disease outcomes in cSCC. The findings of this research offers a clear pathway to determine clinical outcomes based on a patients TME signature. This could also be extended to predicting who should be on immunotherapy and the chances of therapy success.