title: 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: 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).
authors.affiliation: 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.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Oguejiofor
authors.affiliation: 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.
authors.forename: Henry
authors.initials: H
authors.lastname: Galletta-Williams
authors.affiliation: 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.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Dovedi
authors.affiliation: 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.
authors.forename: Darren L
authors.initials: DL
authors.lastname: Roberts
authors.affiliation: 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.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Stern
authors.affiliation: 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.
authors.forename: Catharine M L
authors.initials: CM
authors.lastname: West
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D027383:Papillomaviridae / Q000502:physiology*; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D012189:Retrospective Studies; D015996:Survival Rate; D059016:Tumor Microenvironment; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; D061026:Programmed Cell Death 1 Receptor; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: PD-L1; checkpoint inhibitor; human papillomavirus; oropharyngeal squamous cell carcinomas; tumour infiltrating lymphocytes