Article (Scientific journals)
ITGBL1 is a new immunomodulator that favors development of melanoma tumors by inhibiting natural killer cells cytotoxicity
cheli, yann; tulic, meri; El Hachem, Najla et al.
2021In Molecular Cancer
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Keywords :
melanoma; immunotherapy; itgbl1
Abstract :
[en] Resistances to immunotherapies remains a major hurdle towards a cure for melanoma in numerous patients. An increase in the mesenchymal phenotype and a loss of differentiation have been clearly associated with resistance to targeted therapies. Similar phenotypes have been more recently also linked to resistance to immune checkpoint therapies. We demonstrated here that the loss of MIcrophthalmia associated Transcription Factor (MITF), a pivotal player in melanocyte differentiation, favors the escape of melanoma cells from the immune system. We identified Integrin beta-like protein 1 (ITGBL1), a secreted protein, upregulated in anti-PD1 resistant patients and in MITFlow melanoma cells, as the key immunomodulator. ITGBL1 inhibited immune cell cytotoxicity against melanoma cells by inhibiting NK cells cytotoxicity and counteracting beneficial effects of anti-PD1 treatment, both in vitro and in vivo. Mechanistically, MITF inhibited RUNX2, an activator of ITGBL1 transcription. Interestingly, VitaminD3, an inhibitor of RUNX2, improved melanoma cells to death by immune cells. In conclusion, our data suggest that inhibition of ITGBL1 might improve melanoma response to immunotherapies.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
cheli, yann
tulic, meri
El Hachem, Najla  ;  Université de Liège - ULiège > Stem Cells-Cancer Signaling
nottet, nicolas
Jacquel, Arnaud
Gesson, Maeva
Strub, thomas
bille, karine
picard-gauci, Alexandra
montaudié, henri
beranger, guillaume
passeron, Thierry
Close, Pierre  ;  Université de Liège - ULiège > Stem Cells-Cancer Signaling
Bertolotto, corine
ballotti, robert
More authors (5 more) Less
Language :
English
Title :
ITGBL1 is a new immunomodulator that favors development of melanoma tumors by inhibiting natural killer cells cytotoxicity
Publication date :
07 January 2021
Journal title :
Molecular Cancer
eISSN :
1476-4598
Publisher :
BioMed Central, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 18 January 2021

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