Format

Send to

Choose Destination
Biosci Trends. 2019 Mar 14;13(1):58-69. doi: 10.5582/bst.2019.01003. Epub 2019 Feb 15.

Programmed death ligand-1, tumor infiltrating lymphocytes and HLA expression in Chinese extrahepatic cholangiocarcinoma patients: Possible immunotherapy implications.

Author information

1
School of Clinical Medicine, Tsinghua University.
2
Department of Hepatopancreatobiliary Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University.
3
Department of Hematology and Oncology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University.
4
Department of Pathology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University.

Abstract

Immunotherapy might be an effective treatment in extrahepatic cholangiocarcinoma (eCCA), a tumor with extremely limited therapeutic options. Our study is to characterize the programmed death ligand-1 (PD-L1) protein expression and cancer microenvironment profiles in surgically resected eCCA samples. PD-L1 positivity was observed on tumor cells (32.3%) as well as on tumor-associated macrophages (74.2%). PD-L1 expression by eCCA correlated significantly with immune parameters such as intra-tumoral CD3+ tumor infiltrating lymphocytes (TILs) density (P = 0.002), intra-tumoral CD8+ TILs density (P < 0.001), and the expression pattern of human leukocyte antigen (HLA) class I (P < 0.001). Immunofluorescence showed that PD-L1 positive tumor cells were adjacent to PD-1 positive cells and the stroma covered with interferon-γ. Correlation with clinicopathological parameters and survival analyses revealed that PD-L1 positivity in eCCA was related to the absence of venous invasion (P = 0.030), improved overall survival (P = 0.020) and progressionfree survival (P = 0.011). HLA class I molecules defect, which is an important mechanism of immune evasion, was frequently observed in eCCA (50.0%) and was associated with a decreased number of intra-tumoral CD8+ TIL density (P = 0.028). Additionally, the presence of unusually high numbers of tumor-associated macrophages (TAMs) subsets M2 in most of eCCA (74.2%) was noted. Our study indicated that PD-L1 expression in association with intra-tumoral TILs infiltration and HLA class I expression in 32.3% of the eCCA reflects an active immune microenvironment potentially responsive to PD-1/PD-L1 inhibitors. In addition, the combination of macrophage-targeting agents may provide therapeutic synergy for future immunotherapy.

KEYWORDS:

Extrahepatic cholangiocarcinoma; HLA class I molecules; PD-L1; TAMs; TILs

PMID:
30773525
DOI:
10.5582/bst.2019.01003
Free full text

Supplemental Content

Full text links

Icon for J-STAGE, Japan Science and Technology Information Aggregator, Electronic
Loading ...
Support Center