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

J Hamanishi, M Mandai, M Iwasaki… - Proceedings of the …, 2007 - National Acad Sciences
J Hamanishi, M Mandai, M Iwasaki, T Okazaki, Y Tanaka, K Yamaguchi, T Higuchi, H Yagi…
Proceedings of the National Academy of Sciences, 2007National Acad Sciences
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 …
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.
National Acad Sciences