start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=7
article-no=
start-page=895
end-page=908
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230705
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=High Expression of MHC Class I Overcomes Cancer Immunotherapy Resistance Due to IFNƒÁ Signaling Pathway Defects
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=IFNƒÁ signaling pathway defects are well-known mechanisms of resistance to immune checkpoint inhibitors. However, conflicting data have been reported, and the detailed mechanisms remain unclear. In this study, we have demonstrated that resistance to immune checkpoint inhibitors owing to IFNƒÁ signaling pathway defects may be primarily caused by reduced MHC-I expression rather than by the loss of inhibitory effects on cellular proliferation or decreased chemokine production. In particular, we found that chemokines that recruit effector T cells were mainly produced by immune cells rather than cancer cells in the tumor microenvironment of a mouse model, with defects in IFNƒÁ signaling pathways. Furthermore, we found a response to immune checkpoint inhibitors in a patient with JAK-negative head and neck squamous cell carcinoma whose HLA-I expression level was maintained. In addition, CRISPR screening to identify molecules associated with elevated MHC-I expression independent of IFNƒÁ signaling pathways demonstrated that guanine nucleotide-binding protein subunit gamma 4 (GNG4) maintained MHC-I expression via the NF-ƒÈB signaling pathway. Our results indicate that patients with IFNƒÁ signaling pathway defects are not always resistant to immune checkpoint inhibitors and highlight the importance of MHC-I expression among the pathways and the possibility of NF-ƒÈB?targeted therapies to overcome such resistance.
en-copyright=
kn-copyright=

en-aut-name=KawaseKatsushige
en-aut-sei=Kawase
en-aut-mei=Katsushige
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KawashimaShusuke
en-aut-sei=Kawashima
en-aut-mei=Shusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=InozumeTakashi
en-aut-sei=Inozume
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TanjiEtsuko
en-aut-sei=Tanji
en-aut-mei=Etsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KawazuMasahito
en-aut-sei=Kawazu
en-aut-mei=Masahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=HanazawaToyoyuki
en-aut-sei=Hanazawa
en-aut-mei=Toyoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=2
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=3
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=5
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=6
en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute
kn-affil=

affil-num=7
en-affil=Department of Otorhinolaryngology/Head & Neck Surgery, Graduate School of Medicine, Chiba University
kn-affil=

affil-num=8
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END