Abstract 1636: Increased expression of programmed death-ligand 1 (PD-L1) on infiltrating immune cells of hepatocellular carcinoma (HCC) tissues after sorafenib treatment
Authors: Lu Li-Chun , Lee Yi-Hsuan , Chang Chun-Jung , Shao Yu-Yun , Liu Tsung-hao , Cheng Ann-Lii , Hsu Chih-Hung 
Published: July 2017

Background: PD-L1 expression in tumor microenvironment of HCC was reported to associate with tumor aggressiveness and recurrence. The impact of sorafenib treatment on PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC) of HCC has been unclear.

Patients and Methods: We reviewed patients with HCC who had received sorafenib for advanced diseases at National Taiwan University Hospital, Taipei, Taiwan. Patients with paired HCC tissues, obtained before and after sorafenib treatment, were included. Immunohistochemistry (IHC) assay with clone SP142 antibody (Spring Bioscience, Pleasanton, CA, USA) was performed to analyze PD-L1 expression on TC and IC in paired specimens obtained before and after sorafenib. PD-L1 expression was scored as IHC 0, 1, 2, or 3 if &lt;1%, ≥1% but &lt;5%, ≥5% but &lt;10%, or ≥10% of cells were PD-L1 positive, respectively. Further IHC assay was employed to characterize the PD-L1-positive IC. Associations between the PD-L1 expression and overall survival (OS) or duration of sorafenib treatment of the patients were analyzed.

Results: Twenty-three advanced HCC patients (Male: Female= 20: 3, median age of 64 years) with paired HCC tissues were included. All of the post-sorafenib HCC tissues were obtained after disease progression. The median duration of sorafenib treatment was 4.3 months (range: 1.3 to 18.7). The PD-L1 expression on IC was significantly increased in post-sorafenib HCC tissues, compared with tissues obtained before sorafenib (pre-sorafenib vs post-sorafenib IHC 0/1/2/3: 10/5/5/3 vs 5/5/2/11, p=0.046). However, the PD-L1 expression on TC was not significantly different between pre- and post-sorafenib tissues (IHC 0/1/2/3: 19/2/0/2 vs 14/5/0/4, p=0.065). By using IHC staining of CD68, CD66b, CD11b, and CD3 on the consecutive slides, we found the PD-L1-expressing IC were mainly CD68-positive macrophages, but not neutrophils or T lymphocytes. Neither the PD-L1 expression levels on IC of pre-sorafenib or those of post-sorafenib tissues were associated with OS or duration of sorafenib treatment.

Conclusions: The PD-L1 expression on IC, especially on macrophages, in tumor microenvironment was significantly increased in post-sorafenib progression HCC tissues. Whether this increased PD-L1 expression contributes to treatment failure of sorafenib warrants further investigation (This work was supported by the grants of NTUH 105-M3232 and MOST 105-2314-B-002-180).

Citation Format: Li-Chun Lu, Yi-Hsuan Lee, Chun-Jung Chang, Yu-Yun Shao, Tsung-hao Liu, Ann-Lii Cheng, Chih-Hung Hsu. Increased expression of programmed death-ligand 1 (PD-L1) on infiltrating immune cells of hepatocellular carcinoma (HCC) tissues after sorafenib treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1636. doi:10.1158/1538-7445.AM2017-1636