title: PD-L1 expression in nonclear-cell renal cell carcinoma.
abstract: BACKGROUND
  Programmed death ligand-1 (PD-L1) expression in nonclear-cell RCC (non-ccRCC) and its association with clinical outcomes are unknown.
  
  
  METHODS
  Formalin-fixed paraffin-embedded (FFPE) specimens were obtained from 101 patients with non-ccRCC. PD-L1 expression was evaluated by immunohistochemistry in both tumor cell membrane and tumor-infiltrating mononuclear cells (TIMC). PD-L1 tumor positivity was defined as ≥5% tumor cell membrane staining. For PD-L1 expression in TIMC, a combined score based on the extent of infiltrate and percentage of positive cells was used. Baseline clinico-pathological characteristics and outcome data [time to recurrence (TTR) and overall survival (OS)] were correlated with PD-L1 staining.
  
  
  RESULTS
  Among 101 patients, 11 (10.9%) were considered PD-L1+ in tumor cells: 2/36 (5.6%) of chromophobe RCC, 5/50 (10%) of papillary RCC, 3/10 (30%) of Xp11.2 translocation RCC and 1/5 (20%) of collecting duct carcinoma. PD-L1 positivity (PD-L1+) in tumor cells was significantly associated with higher stage (P = 0.01) and grade (P = 0.03), as well as shorter OS (P < 0.001). On the other hand, PD-L1 positivity by TIMC was observed in 57 (56.4%) patients: 13/36 (36.1%) of chromophobe RCC, 30/50 (60%) of papillary RCC, 9/10 (90%) of Xp11.2 translocation RCC and 5/5 (100%) of collecting duct carcinoma. A trend toward shorter OS was observed in patients with PD-L1+ in TIMC (P = 0.08). PD-L1+ in both tumor cell membrane and TIMC cells were associated with shorter TTR (P = 0.02 and P = 0.03, respectively).
  
  
  CONCLUSIONS
  In non-ccRCC, patients with PD-L1+ tumors appear to have worse clinical outcomes, although only PD-L1 positivity in tumor cells is associated with higher tumor stage and grade.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston; Department of Medical Oncology, Brigham and Women's Hospital, Boston; Harvard Medical School, Boston. Electronic address: toni_choueiri@dfci.harvard.edu.
authors.forename: T K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston.
authors.forename: A P
authors.initials: AP
authors.lastname: Fay
authors.affiliation: Biostatistics and Computational Biology, Harvard School of Public Health, Boston.
authors.forename: K P
authors.initials: KP
authors.lastname: Gray
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston.
authors.forename: M
authors.initials: M
authors.lastname: Callea
authors.affiliation: Department of Medical Oncology, Mayo Clinic, Scottsdale.
authors.forename: T H
authors.initials: TH
authors.lastname: Ho
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston.
authors.forename: L
authors.initials: L
authors.lastname: Albiges
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston; Department of Medical Oncology, Brigham and Women's Hospital, Boston; Harvard Medical School, Boston.
authors.forename: J
authors.initials: J
authors.lastname: Bellmunt
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston.
authors.forename: J
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston.
authors.forename: I
authors.initials: I
authors.lastname: Carvo
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston.
authors.forename: M
authors.initials: M
authors.lastname: Lampron
authors.affiliation: Department of Medical Oncology, Mayo Clinic, Scottsdale.
authors.forename: M L
authors.initials: ML
authors.lastname: Stanton
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston; Harvard Medical School, Boston; Center for Immuno-oncology, Dana-Farber Cancer Institute, Boston.
authors.forename: F S
authors.initials: FS
authors.lastname: Hodi
authors.affiliation: Harvard Medical School, Boston; Department of Medical Oncology, Beth-Israel Deaconess Medical Center, Boston.
authors.forename: D F
authors.initials: DF
authors.lastname: McDermott
authors.affiliation: Department of Medical Oncology, Georgetown-Lombardi Comprehensive Cancer Center, Washington, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Atkins
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston; Harvard Medical School, Boston.
authors.forename: G J
authors.initials: GJ
authors.lastname: Freeman
authors.affiliation: Harvard Medical School, Boston; Department of Pathology, Brigham and Women's Hospital, Boston.
authors.forename: M S
authors.initials: MS
authors.lastname: Hirsch
authors.affiliation: Harvard Medical School, Boston; Department of Pathology, Brigham and Women's Hospital, Boston.
authors.forename: S
authors.initials: S
authors.lastname: Signoretti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human
keywords: PD-1 inhibitors; PD-L1; benign kidney tumors; immunotherapy; nonclear-cell renal cell carcinoma; renal cell carcinoma