Subin Wui^1,2, Rehana V Hewavisenti¹, Mohammad Rabiei^3,4, Anthony Kelleher¹, Mahtab Farzin^5,6,7, Shanmugarajah Rajendra^3,4,8*, Sarah C Sasson¹*

 

¹Immunovirology and Pathogenesis Program, The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia

²School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia

³Gastro-Intestinal Viral Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, Sydney, NSW, Australia

⁴South Western Sydney Clinical School, University of New South Wales, Kensington, Sydney, NSW, Australia

⁵Department of Anatomical Pathology, Liverpool Hospital, Liverpool, NSW, Australia

⁶Department of Pathology, Campbelltown Hospital, Campbelltown, NSW, Australia

⁷Conjoint Lecturer, Western Sydney University, NSW, Australia 

⁸Department of Gastroenterology & Hepatology, Bankstown-Lidcombe Hospital, Bankstown, Sydney, NSW, Australia

 

Introduction: Oesophageal adenocarcinoma (OAC) poses a grave challenge in oncology, with a low 5-year survival rate of approximately 20% and an alarming increase in incidence. Recent evidence suggests that human papillomavirus (HPV), a sexually transmitted oncogenic virus, is associated with 15-35% of OAC. T-cells are critical in driving both anti-viral and anti-tumour responses, however characterisation of T-cell subsets between HPV-driven and HPV-independent OAC has not been well-studied. 

 

Methodology: Multiplex immunofluorescence staining of pan-cytokeratin, CD4, CD8, CD103 and FOXP3 was conducted on HPV-positive (n=15) and HPV-negative (n=22) OAC biopsies. T-cell subset densities were assessed using HALO^® image analysis platform between groups, and the association of T-cell subset densities with overall survival (OS) were evaluated. 

 

Results: T-regulatory cells (Tregs) were higher in HPV-negative OAC compared to HPV-positive OAC. CD8:Treg ratios were significantly lower in the HPV-negative cohort. Shorter OS in patients with high Treg densities and low CD8:Treg ratios were observed. Cox multivariate analyses revealed low total CD8:Treg ratio to be independently associated with poorer prognosis (HR 3.06; 95% CI 1.05-10.27; p=0.050). 

 

Conclusion: This novel work reports evidence of an immunosuppressed tumour microenvironment in HPV-negative OAC and supports the potential of both HPV-positivity and CD8:Treg ratio as potentially useful prognostic biomarkers.  

 

I declare that the research work presented in this abstract is original work, and all contributions have been made by the listed authors.