Oral Presentation COSA 2015 ASM

Density of Foxp3+ regulatory T cells correlates with radioresponsiveness in locally advanced rectal cancer (#21)

Melanie McCoy 1 2 , Chris Hemmings 1 2 3 , Tim Miller 1 2 , Stephanie Austin 1 , Max Bulsara 4 , Nik Zeps 1 2 , Anna Nowak 5 6 , Richard Lake 5 , Cameron Platell 1 2
  1. Cancer Research Group, St John of God, Perth, WA, Australia
  2. School of Surgery, University of Western Australia, Perth, WA, Australia
  3. Anatomic Pathology and Molecular Oncology, St John of God Pathology, Perth, WA, Australia
  4. Institute for Health Research, University of Notre Dame, Fremantle, WA, Australia
  5. School of Medicine and Pharmacology, University of Western Australia, Perth, wa, Australia
  6. Sir Charles Gairdner Hospital, Perth, WA, Australia

Background: Pathologic complete response (pCR) following neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer is associated with a reduced risk of recurrence and improved long-term survival.  While approximately 20% of patients achieve a pCR, around 40% experience little or no tumour regression, and factors that distinguish responders from non-responders are currently poorly understood.

Foxp3+ regulatory T cells (Tregs) play a vital role in preventing autoimmunity, but also suppress anti-tumour immune responses.  Tumour infiltration by Tregs has strong prognostic significance in colorectal cancer, and accumulating evidence suggests that chemotherapy and radiotherapy efficacy has an immune-mediated component.  Whether Tregs affect response to CRT in rectal cancer remains unknown. 

Aim: To determine whether the presence of Tregs in the tumour microenvironment following neaoadjuvant CRT is associated with treatment response.

Methods: Representative areas of residual tumour, stroma and normal epithelium from 128 consecutive cases of neoadjuvantly-treated rectal cancer were assessed for infiltration of Foxp3+ cells using standard immunohistochemistry.  Response to CRT was assessed using the Dworak grading system.

Results: Stromal Foxp3+ cell density was strongly associated with tumour regression grade (P = 0.0006).   A low stromal Foxp3+ cell density was observed in 84% of patients who had a pCR compared to 41% of patients who did not (OR: 7.56, P = 0.0005; OR: 5.27, P = 0.006 after adjustment for pre-surgery clinical factors).  Low stromal Foxp3+ cell density was also associated with improved recurrence-free survival (HR: 0.46, P = 0.03), albeit not independent of tumour regression grade.

Conclusion: Tregs in the tumour microenvironment may inhibit response to neoadjuvant-CRT and may represent a therapeutic target in rectal cancer.