Programmed cell death 1 ligand 1 and tumor-infiltrating CD8⁺ T lymphocytes are prognostic factors of human ovarian cancer

• Published in: Proceedings of the National Academy of Sciences - PNAS 2007-02, Vol.104 (9), p.3360-3365
• Main Authors: Hamanishi, Junzo, Mandai, Masaki, Iwasaki, Masashi, Okazaki, Taku, Tanaka, Yoshimasa, Yamaguchi, Ken, Higuchi, Toshihiro, Yagi, Haruhiko, Takakura, Kenji, Minato, Nagahiro, Honjo, Tasuku, Fujii, Shingo
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies - immunology; Antibodies - metabolism; Antigens; Antigens, CD - immunology; Antigens, CD - metabolism; Apoptosis; B7-H1 Antigen; Biological Sciences; Cancer; CD8-Positive T-Lymphocytes - immunology; Cells; Correlations; Disease free survival; Female; Gene expression; Humans; Immunity; Immunohistochemistry; Ligands; Lymphocyte Count; Lymphocytes; Metastasis; Middle Aged; Multivariate Analysis; Ovarian cancer; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - immunology; Ovarian Neoplasms - pathology; Prognosis; Reproductive system; T lymphocytes; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0611533104

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.