Overexpression of PD-L1 Significantly Associates with Tumor Aggressiveness and Postoperative Recurrence in Human Hepatocellular Carcinoma.
Clin Cancer Res. 2009 Feb 1;15(3):971-979.
Gao Q, Wang XY, Qiu SJ, Yamato I, Sho M, Nakajima Y, Zhou J, Li BZ, Shi YH, Xiao YS, Xu Y, Fan J.
Authors' Affiliations: Liver Cancer Institute, Zhong Shan Hospital and Shanghai Medical School, Department of Pathology, Cancer Hospital, and Institute of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China and Department of Surgery, Nara Medical University, Nara, Japan.
PURPOSE:
The aberrant expression of programmed cell death 1 ligands 1 and 2 (PD-Ls) on tumor cells dampens antitumor immunity, resulting in tumor immune evasion. In this study, we investigated the expression of PD-Ls in human hepatocellular carcinoma (HCC) to define their prognostic significance after curative surgery.
EXPERIMENTAL DESIGN:
Immunohistochemistry was used to investigate PD-Ls expression as well as granzyme B(+) cytotoxic and FoxP3(+) regulatory T cell infiltration on tissue microarrays containing 240 randomly selected HCC patients who underwent surgery. The results were further verified in an independent cohort of 125 HCC patients. PD-Ls expression on HCC cell lines was detected by Western blot assay.
RESULTS:
Patients with higher expression of PD-L1 had a significantly poorer prognosis than patients with lower expression. Although patients with higher expression of PD-L2 also had a poorer survival, the difference in recurrence was not statistically significant. Multivariate analysis identified tumor expression of PD-L1 as an independent predictor for postoperative recurrence. No correlation was found between PD-Ls expression and granzyme B(+) lymphocyte infiltration, whereas a significant positive correlation was detected between PD-Ls expression and FoxP3(+) lymphocyte infiltration. In addition, tumor-infiltrating cytotoxic and regulatory T cells were also independent prognosticators for both survival and recurrence. The prognostic value of PD-L1 expression was validated in the independent data set.
CONCLUSION:
Our data suggest for the first time that PD-L1 status may be a new predictor of recurrence for HCC patients and provide the rationale for developing a novel therapy of targeting the PD-L1/PD-1 pathway against this fatal malignancy. |
