title: Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer.
abstract: The ligands for programmed cell death 1 (PD-1), an immunoinhibitory receptor belonging to CD28/cytotoxic T lymphocyte antigen 4 family, are PD-1 ligand 1 and 2 (PD-Ls). Recent reports suggest that the aberrant expression of PD-Ls on tumor cells impairs antitumor immunity, resulting in the immune evasion of the tumor cells. Although an inverse correlation between the expression level of PD-Ls and patients' prognosis has been reported for several malignant tumors, the follow-up period was limited because of the lack of the antibody (Ab) applicable to paraffin-embedded specimens. Here we generated a new Ab against PD-1 ligand 1 (PD-L1) and analyzed the expression level of PD-Ls in human ovarian cancer using paraffin-embedded specimens. Patients with higher expression of PD-L1 had a significantly poorer prognosis than patients with lower expression. Although patients with higher expression of PD-1 ligand 2 also had a poorer prognosis, the difference was not statistically significant. A significant inverse correlation was observed between PD-L1 expression and the intraepithelial CD8(+) T lymphocyte count, suggesting that PD-L1 on tumor cells directly suppresses antitumor CD8(+) T cells. Multivariate analysis showed the expression of PD-L1 on tumor cells and intraepithelial CD8(+) T lymphocyte count are independent prognostic factors. The PD-1/PD-L pathway can be a good target for restoring antitumor immunity in ovarian cancer.
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Junzo
authors.initials: J
authors.lastname: Hamanishi
authors.forename: Masaki
authors.initials: M
authors.lastname: Mandai
authors.forename: Masashi
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Taku
authors.initials: T
authors.lastname: Okazaki
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Higuchi
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Yagi
authors.forename: Kenji
authors.initials: K
authors.lastname: Takakura
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Minato
authors.forename: Tasuku
authors.initials: T
authors.lastname: Honjo
authors.forename: Shingo
authors.initials: S
authors.lastname: Fujii
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D060890:B7-H1 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018655:Lymphocyte Count; D008875:Middle Aged; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000276:immunology* / Q000473:pathology; D011379:Prognosis
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human