PMID- 30773525
OWN - NLM
STAT- MEDLINE
DCOM- 20190628
LR  - 20190628
IS  - 1881-7823 (Electronic)
IS  - 1881-7815 (Linking)
VI  - 13
IP  - 1
DP  - 2019 Mar 14
TI  - Programmed death ligand-1, tumor infiltrating lymphocytes and HLA expression in 
      Chinese extrahepatic cholangiocarcinoma patients: Possible immunotherapy 
      implications.
PG  - 58-69
LID - 10.5582/bst.2019.01003 [doi]
AB  - 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-gamma. 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.
FAU - Yu, Fei
AU  - Yu F
AD  - School of Clinical Medicine, Tsinghua University.
FAU - Gong, Lei
AU  - Gong L
AD  - Department of Hepatopancreatobiliary Surgery, Beijing Tsinghua Changgung 
      Hospital, School of Clinical Medicine, Tsinghua University.
FAU - Mo, Zheng
AU  - Mo Z
AD  - Department of Hematology and Oncology, Beijing Tsinghua Changgung Hospital, 
      School of Clinical Medicine, Tsinghua University.
FAU - Wang, Wenran
AU  - Wang W
AD  - School of Clinical Medicine, Tsinghua University.
AD  - Department of Hepatopancreatobiliary Surgery, Beijing Tsinghua Changgung 
      Hospital, School of Clinical Medicine, Tsinghua University.
FAU - Wu, Meilong
AU  - Wu M
AD  - School of Clinical Medicine, Tsinghua University.
AD  - Department of Hepatopancreatobiliary Surgery, Beijing Tsinghua Changgung 
      Hospital, School of Clinical Medicine, Tsinghua University.
FAU - Yang, Jianghui
AU  - Yang J
AD  - Department of Pathology, Beijing Tsinghua Changgung Hospital, School of Clinical 
      Medicine, Tsinghua University.
FAU - Zhang, Qiongqiong
AU  - Zhang Q
AD  - School of Clinical Medicine, Tsinghua University.
FAU - Li, Li
AU  - Li L
AD  - Department of Pathology, Beijing Tsinghua Changgung Hospital, School of Clinical 
      Medicine, Tsinghua University.
FAU - Yao, Jingjing
AU  - Yao J
AD  - Department of Pathology, Beijing Tsinghua Changgung Hospital, School of Clinical 
      Medicine, Tsinghua University.
FAU - Dong, Jiahong
AU  - Dong J
AD  - School of Clinical Medicine, Tsinghua University.
LA  - eng
PT  - Journal Article
DEP - 20190215
PL  - Japan
TA  - Biosci Trends
JT  - Bioscience trends
JID - 101502754
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
SB  - IM
MH  - Aged, 80 and over
MH  - B7-H1 Antigen/*metabolism
MH  - Bile Duct Neoplasms/immunology/*metabolism/mortality/pathology
MH  - China/epidemiology
MH  - Cholangiocarcinoma/immunology/*metabolism/mortality/pathology
MH  - Cohort Studies
MH  - Female
MH  - Humans
MH  - Lymphocytes, Tumor-Infiltrating/physiology
MH  - Macrophages/metabolism
MH  - Male
MH  - Middle Aged
MH  - Tumor Microenvironment
MH  - Young Adult
OTO - NOTNLM
OT  - Extrahepatic cholangiocarcinoma
OT  - HLA class I molecules
OT  - PD-L1
OT  - TAMs
OT  - TILs
EDAT- 2019/02/19 06:00
MHDA- 2019/06/30 06:00
CRDT- 2019/02/19 06:00
PHST- 2019/02/19 06:00 [pubmed]
PHST- 2019/06/30 06:00 [medline]
PHST- 2019/02/19 06:00 [entrez]
AID - 10.5582/bst.2019.01003 [doi]
PST - ppublish
SO  - Biosci Trends. 2019 Mar 14;13(1):58-69. doi: 10.5582/bst.2019.01003. Epub 2019 
      Feb 15.