Tumour-infiltrating regulatory T cell density before neoadjuvant chemoradiotherapy for rectal cancer does not predict treatment response

// Melanie J. McCoy 1, 4 , Chris Hemmings 2, 3 , Chidozie C. Anyaegbu 1 , Stephanie J. Austin 1, 3 , Tracey F. Lee-Pullen 1, 3 , Timothy J. Miller 1, 3 , Max K. Bulsara 5 , Nikolajs Zeps 1, 3 , Anna K. Nowak 4, 6 , Richard A. Lake 4 , Cameron F. Platell 1, 3 1 Colorectal Research Unit, St John of God Subiaco Hospital, Subiaco, WA, 6008, Australia 2 Department of Anatomic Pathology, St John of God Pathology, Wembley, WA, 6014, Australia 3 School of Surgery, University of Western Australia, Crawley, WA, 6009, Australia 4 School of Medicine and Pharmacology, University of Western Australia, Crawley, WA, 6009, Australia 5 Institute for Health Research, University of Notre Dame, Fremantle, WA, 6959, Australia 6 Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia Correspondence to: Melanie McCoy, email: melanie.mccoy@uwa.edu.au Keywords: rectal cancer, regulatory T cells, radiotherapy, chemotherapy, treatment response Received: September 13, 2016      Accepted: January 07, 2017      Published: February 03, 2017 ABSTRACT Neoadjuvant (preoperative) chemoradiotherapy (CRT) decreases the risk of rectal cancer recurrence and reduces tumour volume prior to surgery. However, response to CRT varies considerably between individuals and factors associated with response are poorly understood. Foxp3 + regulatory T cells (Tregs) inhibit anti-tumour immunity and may limit any response to chemotherapy and radiotherapy. We have previously reported that a low density of Tregs in the tumour stroma following neoadjuvant CRT for rectal cancer is associated with improved tumour regression. Here we have examined the association between Treg density in pre-treatment diagnostic biopsy specimens and treatment response, in this same patient cohort. We aimed to determine whether pre-treatment tumour-infiltrating Treg density predicts subsequent response to neoadjuvant CRT. Foxp3 + , CD8 + and CD3 + cell densities in biopsy samples from 106 patients were assessed by standard immunohistochemistry (IHC) and evaluated for their association with tumour regression grade and survival. We found no association between the density of any T cell subset pre-treatment and clinical outcome, indicating that tumour-infiltrating Treg density does not predict response to neoadjuvant CRT in rectal cancer. Taken together with the findings of the previous study, these data suggest that in the context of neoadjuvant CRT for rectal cancer, the impact of chemotherapy and/or radiotherapy on anti-tumour immunity may be more important than the state of the pre-existing local immune response.