Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer.
OBJECTIVE
The negative regulatory programmed death-1/programmed death-1 ligand (PD-1/PD-L) pathway in T-cell activation has been suggested to play an important role in tumor evasion from host immunity. In this study, we investigated the expression of PD-L1 and PD-L2 in human esophageal cancer to define their clinical significance in patients' prognosis after surgery.


METHODS
PD-L1 and PD-L2 gene expression was evaluated in 41 esophagectomy patients by real-time quantitative PCR. The protein expression was also evaluated with newly generated monoclonal antibodies that recognize human PD-L1 (MIH1) and PD-L2 (MIH18).


RESULTS
The protein and the mRNA levels of determination by immunohistochemistry and real-time quantitative PCR were closely correlated. PD-L-positive patients had a significantly poorer prognosis than the negative patients. This was more pronounced in the advanced stage of tumor than in the early stage. Furthermore, multivariate analysis indicated that PD-L status was an independent prognostic factor. Although there was no significant correlation between PD-L1 expression and tumor-infiltrating T lymphocytes, PD-L2 expression was inversely correlated with tumor-infiltrating CD8(+) T cells.


CONCLUSIONS
These data suggest that PD-L1 and PD-L2 status may be a new predictor of prognosis for patients with esophageal cancer and provide the rationale for developing novel immunotherapy of targeting PD-1/PD-L pathway.
Ohigashi
Yuichiro
Y
Department of Surgery, Nara Medical University School of Medicine, Nara, Japan.
Sho
Masayuki
M
Yamada
Yukishige
Y
Tsurui
Yoshikazu
Y
Hamada
Kaoru
K
Ikeda
Naoya
N
Mizuno
Takashi
T
Yoriki
Ryo
R
Kashizuka
Hisanori
H
Yane
Katsunari
K
Tsushima
Fumihiko
F
Otsuki
Noriko
N
Yagita
Hideo
H
Azuma
Miyuki
M
Nakajima
Yoshiyuki
Y
D000368:Aged; D015703:Antigens, CD; D018122:B7-1 Antigen / Q000032:analysis / Q000235:genetics*; D060890:B7-H1 Antigen; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004947:Esophagus / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D010455:Peptides / Q000032:analysis / Q000235:genetics*; D011379:Prognosis; D061027:Programmed Cell Death 1 Ligand 2 Protein; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis
D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C556977:PDCD1LG2 protein, human; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; D012333:RNA, Messenger