title: Predictive relevance of PD-L1 expression combined with CD8+ TIL density in stage III non-small cell lung cancer patients receiving concurrent chemoradiotherapy.
abstract: BACKGROUND
  Expression of programmed cell death-ligand 1 (PD-L1) is known to be a mechanism whereby cancer can escape immune surveillance, but little is known about factors predictive of efficacy in patients with locally advanced non-small cell lung cancer (NSCLC). We investigated the predictive relevance of PD-L1 expression and CD8+ tumour-infiltrating lymphocytes (TILs) density in patients with locally advanced NSCLC receiving concurrent chemoradiotherapy (CCRT).
  
  
  METHODS
  We retrospectively reviewed 74 consecutive patients with stage III NSCLC who had received CCRT. PD-L1 expression and CD8+ TIL density were evaluated by immunohistochemical analysis.
  
  
  RESULTS
  Univariate and multivariate analyses demonstrated that CD8+ TIL density was an independent and significant predictive factor for progression-free survival (PFS) and OS, whereas PD-L1 expression was not correlated with PFS and OS. Sub-analysis revealed that the PD-L1+/CD8 low group had the shortest PFS (8.6 months, p = 0.02) and OS (13.9 months, p = 0.11), and that the PD-L1-/CD8 high group had the longest prognosis (median PFS and OS were not reached) by Kaplan-Meier curves of the four sub-groups.
  
  
  CONCLUSIONS
  Among stage III NSCLC patients who received CCRT, there was a trend for poor survival in those who expressed PD-L1. Our analysis indicated that a combination of lack of PD-L1 expression and CD8+ TIL density was significantly associated with favourable survival in these patients. It is proposed that PD-L1 expression in combination with CD8+ TIL density could be a useful predictive biomarker in patients with stage III NSCLC.
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Tokito
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan. Electronic address: azuma@med.kurume-u.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Azuma
authors.affiliation: Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Fukuoka, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kawahara
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Matsuo
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Division of Thoracic Surgery, Yame General Hospital, Yame, Fukuoka, Japan.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Mizukami
authors.affiliation: Division of Radiation Oncology, Yame General Hospital, Yame, Fukuoka, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ono
authors.affiliation: Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Fukuoka, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kage
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human
keywords: CD8+ TIL; PD-L1; chemoradiotherapy; immunohistochemistry; non-small cell lung cancer