PMID- 25154680
OWN - NLM
STAT- MEDLINE
DCOM- 20141217
LR  - 20211021
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 105
IP  - 10
DP  - 2014 Oct
TI  - Inhibition of mitogen-activated protein kinase pathway can induce upregulation of 
      human leukocyte antigen class I without PD-L1-upregulation in contrast to 
      interferon-gamma treatment.
PG  - 1236-44
LID - 10.1111/cas.12503 [doi]
AB  - Recently, we reported that human leukocyte antigen (HLA) class I expression is 
      predominantly regulated by the mitogen-activated protein kinase (MAPK) pathway as 
      one of the oncogenic regulations of HLA class I expression. In the present study, 
      we examined mechanisms of how HLA class I and PD-L1 are regulated by MAPK 
      inhibitors and interferon-gamma (IFN-gamma). Furthermore, we evaluated the expression of 
      major signal transduction molecules by Western blot and anti-tumor CTL activity 
      by a cytotoxic assay when HLA class I and PD-L1 were modulated by MAPK inhibitors 
      and/or IFN-gamma. As a result, we confirmed, as a more general phenomenon, that the 
      inhibition of MAPK could upregulate HLA class I expression in a panel of human 
      solid tumors (n = 26). Of note, we showed that MAPK inhibitors act on the 
      upregulation of HLA class I expression through a different pathway from IFN-gamma; 
      there was an additive effect in the upregulation of HLA class I when treated with 
      the combination of MAPK inhibitors and IFN-gamma, and there was no overlapping 
      activation of JAK2/STAT1 and Erk1/2 molecules when treated with either IFN-gamma or 
      MAPK inhibitors. Furthermore, we showed that IFN-gamma-treatment impaired the 
      tumor-specific CTL activity due to the upregulation of PD-L1 in spite of the 
      upregulation of HLA class I, while MAPK inhibitors can augment the tumor-specific 
      CTL activity due to the upregulated HLA class I without PD-L1 alterations. In 
      conclusion, in addition to the original anti-proliferative activity, MAPK 
      inhibitors may work toward the enhancement of T-cell-mediated anti-tumor immunity 
      through the upregulation of HLA class I without the upregulation of PD-L1.
CI  - (c) 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on 
      behalf of Japanese Cancer Association.
FAU - Mimura, Kousaku
AU  - Mimura K
AD  - Department of Surgery, National University of Singapore, Singapore City, 
      Singapore.
FAU - Kua, Ley-Fang
AU  - Kua LF
FAU - Shiraishi, Kensuke
AU  - Shiraishi K
FAU - Kee Siang, Lim
AU  - Kee Siang L
FAU - Shabbir, Asim
AU  - Shabbir A
FAU - Komachi, Mayumi
AU  - Komachi M
FAU - Suzuki, Yoshiyuki
AU  - Suzuki Y
FAU - Nakano, Takashi
AU  - Nakano T
FAU - Yong, Wei-Peng
AU  - Yong WP
FAU - So, Jimmy
AU  - So J
FAU - Kono, Koji
AU  - Kono K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140929
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
RN  - 0 (Flavonoids)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 82115-62-6 (Interferon-gamma)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - B7-H1 Antigen/analysis/*physiology
MH  - Cell Line, Tumor
MH  - Flavonoids/pharmacology
MH  - Histocompatibility Antigens Class I/*physiology
MH  - Humans
MH  - Interferon-gamma/*pharmacology
MH  - Killer Cells, Natural/immunology
MH  - MAP Kinase Signaling System/drug effects/*physiology
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Up-Regulation
PMC - PMC4462358
OTO - NOTNLM
OT  - Cytotoxic T lymphocyte
OT  - PD-L1
OT  - human leukocyte antigen-A
OT  - interferon-gamma
OT  - mitogen-activated protein kinase
EDAT- 2014/08/27 06:00
MHDA- 2014/12/18 06:00
PMCR- 2014/10/01
CRDT- 2014/08/27 06:00
PHST- 2014/06/02 00:00 [received]
PHST- 2014/08/05 00:00 [revised]
PHST- 2014/08/07 00:00 [accepted]
PHST- 2014/08/27 06:00 [entrez]
PHST- 2014/08/27 06:00 [pubmed]
PHST- 2014/12/18 06:00 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - 10.1111/cas.12503 [doi]
PST - ppublish
SO  - Cancer Sci. 2014 Oct;105(10):1236-44. doi: 10.1111/cas.12503. Epub 2014 Sep 29.