간세포암종에서 2종류 PD-L1과 C-MET발현의 의의

Abstract

Programmed cell death ligand 1 (PD-L1) is an essential immune checkpoint protein for immune evasion of malignant tumor. Also, the overexpression of programmed cell death protein 1 (PD-1) and PD-L1 has been associated with poor prognosis in many cancers. In recent years, there have been advances in cancer immunotherapy and the blocking of the binding between the PD-1 and PD-L1 has been investigated and utilized as the primary target for anti-tumor immunotherapies. In diagnostic pathology, it is crucial to detect the PD-L1 positive cases with a validated immunohistochemistry (IHC) in malignant tumor including lung cancer and urinary bladder cancer. Preliminary data show that C-MET promotes survival of some cancers such as renal cancer through the regulation of PD-L1. However, the expression and the relationship for PD-L1 in Hepatocellular carcinoma (HCC) have not been well characterized and no immunotherapeutic option is currently available for HCC in Korea. Therefore, it is crucial to investigate the expression of PD-L1 and C-MET and their association with clinicopathologic factors to develop targeted treatments for HCC. This study was aimed to examine the expression of PD-L1 in tumor cells (TC) and immune cells (IC) of 70 HCC samples using IHC. This study utilized two clones of anti-PD-L1 antibodies (Abs), SP263 and SP142, which are currently commercially-approved for quantifying PD-L1 expression for lung cancer and urinary bladder cancer. And, This study assessed the expression of C-MET in TC. In addition, This study examined the correlation between expression of two clones of PD-L1 and clinicopathologic factors. The SP263 PD-L1 identified more positive cases compared with the SP142 PD-L1 in both TC and IC; for TC, there were 14/70 positive cases by SP263 but only 2/70 positive cases by SP142. For IC, 49/70 (SP263) and 30/70 (SP142) cases were immuno-reactive for PD-L1 expression. For each clone of anti-PD-L1 Ab, the expression of PD-L1 were much higher in IC than those in TC. Of several clinicopathologic factors, Edmondson–Steiner grade was statistically related to high expression level of SP263 PD-L1 in TC. This study also investigated the C-MET expression and the correlation of its expression with other clinicopathologic factors. C-MET was significantly associated with advanced T stage. C-MET expression was positively related to SP263 PD-L1 expression in TC. These results suggest that C-MET plays a role in regulating PD-L1 expression in HCC. Identification of PD-L1 positive cases using two different clones of anti-PD-L1 Abs was generally comparable in 70 HCC samples. These results would be helpful in providing background data for developing targeted immunotherapy of HCC using PD-L1 or C-MET and for evaluating selection criteria of target population for such treatments.