title: PD-L1 and HLA Class I Antigen Expression and Clinical Course of the Disease in Intrahepatic Cholangiocarcinoma.
abstract: OBJECTIVE
  More effective therapy is needed for intrahepatic cholangiocarcinoma (ICC). The encouraging clinical results obtained with checkpoint molecule-specific monoclonal antibodies (mAb) have prompted us to investigate whether this type of immunotherapy may be applicable to ICC. The aims of this study were to determine whether (i) patients mount a T-cell immune response to their ICC, (ii) checkpoint molecules are expressed on both T cells and tumor cells, and (iii) tumor cells are susceptible to recognition by cognate T cells.
  
  
  METHODS
  Twenty-seven ICC tumors were analyzed for (i) lymphocyte infiltrate, (ii) HLA class I and HLA class II expression, and (iii) PD-1 and PD-L1 expression by T cells and ICC cells, respectively. The results of this analysis were correlated with the clinicopathologic characteristics of the patients investigated.
  
  
  RESULTS
  Lymphocyte infiltrates were identified in all tumors. PD-L1 expression and HLA class I antigen expression by ICC cells was observed in 8 and 11, respectively, of the 27 tumors analyzed. HLA class I antigen expression correlated with CD8(+) T-cell infiltrate. Furthermore, positive HLA class I antigen expression in combination with negative/rare PD-L1 expression was associated with favorable clinical course of the disease.
  
  
  CONCLUSIONS
  ICC patients are likely to mount a T-cell immune response against their own tumors. Defects in HLA class I antigen expression in combination with PD-L1 expression by ICC cells provide them with an immune escape mechanism. This mechanism justifies the implementation of immunotherapy with checkpoint molecule-specific mAbs in patients bearing ICC tumors without defects in HLA class I antigen expression.
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Francesco
authors.initials: F
authors.lastname: Sabbatino
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Villani
authors.affiliation: Merck Research Laboratories, Palo Alto, California.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Yearley
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Vikram
authors.initials: V
authors.lastname: Deshpande
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Ioannis T
authors.initials: IT
authors.lastname: Konstantinidis
authors.affiliation: Merck Research Laboratories, Palo Alto, California.
authors.forename: Christina
authors.initials: C
authors.lastname: Moon
authors.affiliation: Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Nota
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Al-Sukaini
authors.affiliation: Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Andrew X
authors.initials: AX
authors.lastname: Zhu
authors.affiliation: Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Lipika
authors.initials: L
authors.lastname: Goyal
authors.affiliation: Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: David T
authors.initials: DT
authors.lastname: Ting
authors.affiliation: Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Nabeel
authors.initials: N
authors.lastname: Bardeesy
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Hong
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez-del Castillo
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Tanabe
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Lillemoe
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. cferrone@mgh.harvard.edu.
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Ferrone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D060890:B7-H1 Antigen / Q000276:immunology*; D001650:Bile Duct Neoplasms / Q000276:immunology*; D001653:Bile Ducts, Intrahepatic / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018281:Cholangiocarcinoma / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D015395:Histocompatibility Antigens Class I