start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=10
article-no=
start-page=2491
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210520
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Cripto-1 as a Potential Target of Cancer Stem Cells for Immunotherapy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Simple Summary Cancer immunotherapy is gaining attention as a potential fourth treatment following surgery, chemotherapy, and radiation therapy. Cancer stem cells have recently been recognized and validated as a key target for cancer treatment. Cripto-1, which is a GPI-anchored membrane-bound protein that functions as a co-receptor of Nodal, is a marker of cancer stem cells. Since Nodal is a member of the TGF-beta family, which performs an important role in stem cells and cancer stem cells, the inhibition of Cripto-1 could be a strategy by which to block Nodal signaling and thereby suppress cancer stem cells. We propose that Cripto-1 may be a novel target for cancer immunotherapy. The immune system has been found to be suppressed in cancer patients. Cancer cells are extremely resistant to chemotherapeutic drugs, conventional immunotherapy, or cancer antigen vaccine therapy. Cancer immunotherapy, which is mainly based on immune checkpoint inhibitors, such as those for PD-1, PD-L1, and CTLA4, is an effective treatment method. However, no immunotherapeutic target has been found that retains validity in the face of tumor diversity. The transforming growth factor (TGF)-beta cytokine family possesses broad biological activity and is involved in the induction and/or transdifferentiation of helper T cells, which are important in immunotherapy. Nodal is a member of the TGF-beta family playing important roles in tissue stem cells and cancer stem cells (CSCs), interacting with the co-receptor Cripto-1, as well as with Activin type IB (Alk4) and Activin typeIIreceptors, and maintaining stemness and Notch and Wnt/beta-catenin signaling in CSCs. In recent years, it has been reported that Cripto-1 could be a potential therapeutic target in CSCs. Here, we review the accumulated literature on the molecular mechanisms by which Cripto-1 functions in CSCs and discuss the potential of Cripto-1 as an immunotherapeutic target in CSCs.
en-copyright=
kn-copyright=

en-aut-name=IshiiHiroko
en-aut-sei=Ishii
en-aut-mei=Hiroko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SalomonDavid S.
en-aut-sei=Salomon
en-aut-mei=David S.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SenoMasaharu
en-aut-sei=Seno
en-aut-mei=Masaharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=GSP Enterprise, Inc.
kn-affil=

affil-num=2
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=3
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=4
en-affil=Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute
kn-affil=

affil-num=5
en-affil=
kn-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
en-keyword=Cripto-1
kn-keyword=Cripto-1
en-keyword=TGF-beta
kn-keyword=TGF-beta
en-keyword=cancer stem cells
kn-keyword=cancer stem cells
en-keyword=immunotherapy
kn-keyword=immunotherapy
en-keyword=antibody
kn-keyword=antibody
END