Oral Presentation NSW State Cancer Conference 2023

Immune predictors of response to immunotherapy in metastatic cSCC (#10)

Benjamin Genenger 1 2 , Amarinder Thind 1 2 , Sarbar Napaki 3 4 5 , Jay R Perry 1 2 , Bruce Ashford 2 3 , Marie Ranson 1 2 , Daniel Brungs 1 2 3 6
  1. Molecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, Australia
  2. Illawarra Health and Medical Research Institute, Wollongong, NSW, Australia
  3. Graduate School of Medicine, University of Wollongong, Wollongong, NSW, Australia
  4. Anatomical Pathology, Wollongong Hospital, Wollongong, NSW, Australia
  5. Southern IML Pathology/ Sonic Healthcare, Wollongong, NSW, Australia
  6. Illawarra Cancer Centre, Wollongong Hospital, Wollongong, NSW, Australia

Introduction:

Cutaneous squamous cell carcinoma (cSCC) is a very common skin malignancy that develops metastases in up to 5% of cases. While early stage cSCC can often be cured by local surgical resection, locally advanced and metastatic cSCC requires aggressive multimodal therapy. Prior to the introduction of immune checkpoint inhibitors, locally advanced disease required debilitating surgery and radiotherapy, and oligometastatic disease was universally fatal. Cemiplimab, an immune checkpoint inhibitor (ICI), demonstrated 47% overall response rate and received FDA approval for locally advanced or metastatic cSCC in 2018. To date, the ICI cemiplimab and pembrolizumab remain the only systemic therapies approved for cSCC not amenable for curative surgery or radiotherapy. However, there are currently no prognostic biomarkers available to predict ICI treatment outcome and the biology dictating therapy outcome remains poorly understood. In this study, we explore the expression of immune-related markers in one of the first cohort of patients with metastatic and advanced cSCC treated with immunotherapy.

Materials and Methods:

RNA was extracted from representative areas of cSCC tumors in FFPE samples of patients with advanced or metastatic cSCC who had undergone treatment with ICI targeting PD-L1/PD-1 and had responded or not responded. The gene expression of 770 immune-related genes was determined using the nCounter PanCancer IO 360 panel ™ (Nanostring, USA). Differential gene expression analysis was performed using DEseq2. CIBERSORTx digital cytometry was used to estimate the immune cell fractions.

Result and Discussion:

Firstly, we explored the differential gene expression of responders versus non-responders to immune checkpoint inhibitors. Preliminary results suggest the increased expression of L-Selectin, a cell adhesion molecule with a role in tumor immunity, in non-responding patients. Digital spatial profiling of responders highlighted the relevance of the tumour immune microenvironment and its utility in prognosis.

Conclusion:

In conclusion, this work provides a first indication for potential biomarkers and factors that govern the response to immune checkpoint inhibition in cSCC.