Distinct patterns of infiltrating CD8+ T cells in HPV+ and CD68 macrophages in HPV- oropharyngeal squamous cell carcinomas are associated with better clinical outcome but PD-L1 expression is not prognostic

Abstract

// Kenneth Oguejiofor 1 , Henry Galletta-Williams 1 , Simon J. Dovedi 2 , Darren L. Roberts 1 , Peter L. Stern 3 and Catharine M.L. West 1 1 Translational Radiobiology Group, Division of Molecular & Clinical Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Christie Hospital NHS Trust, Manchester, UK 2 Targeted Therapy Group, Division of Molecular & Clinical Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Christie Hospital NHS Trust, Manchester, UK 3 Immunology/Children’s Cancer Group, Division of Molecular & Clinical Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Christie Hospital NHS Trust, Manchester, UK Correspondence to: Peter L. Stern, email: // Keywords : checkpoint inhibitor, PD-L1, human papillomavirus, oropharyngeal squamous cell carcinomas, tumour infiltrating lymphocytes Received : January 10, 2017 Accepted : January 11, 2017 Published : January 22, 2017 Abstract Immunotherapies are beginning to revolutionise treatment paradigms in oncology with monoclonal antibodies (mAb) targeting T-cell co-inhibitory (e.g. PD-1/PD-L1) and co-stimulatory pathways (e.g. CTLA-4/CD28) demonstrating clinical utility. Some clinical studies demonstrate that responsiveness to PD-1/PD-L1 mAb therapy is greater in patients with expression of PD-L1 in the tumour microenvironment. However, robust responses have also been observed in patients with low or absent expression of PD-L1. Using multiplex immuno-fluorescent labelling we sought to determine how infiltration of tumours by CD8 + T-cells, their expression of PD-1, and the expression of PD-L1 on both tumours and CD68 cells (macrophages) correlated with HPV status and outcome in a cohort of 124 oropharyngeal squamous cell carcinomas (OPSCC).