TY - JOUR
T1 - Impact of hypoxic tumor microenvironment and tumor cell plasticity on the expression of immune checkpoints
AU - Lequeux, Audrey
AU - Noman, Muhammad Zaeem
AU - Xiao, Malina
AU - Sauvage, Delphine
AU - Van Moer, Kris
AU - Viry, Elodie
AU - Bocci, Irene
AU - Hasmim, Meriem
AU - Bosseler, Manon
AU - Berchem, Guy
AU - Janji, Bassam
N1 - Funding Information:
This work was supported by the Luxembourg National Research Fund (C18/BM/12670304/COMBATIC), and grants from FNRS Televie (7.4664.15; 7.4565.17; and 7.6505.18), National Research Fund Luxembourg (grant no. FNR PRIDE15/10675146/CANBIO), Luxembourg Institute of Health (LECR 20170540), “Fondation Cancer”, Luxembourg FC/2018/06; Kriibskrank Kanner Foundation, Janssen Cilag 2018 and Action LIONS Vaincre le Cancer, Luxembourg.
Funding Information:
This work was supported by the Luxembourg National Research Fund ( C18/BM/12670304/COMBATIC ), and grants from FNRS Televie ( 7.4664.15; 7.4565.17 ; and 7.6505.18 ), National Research Fund Luxembourg (grant no. FNR PRIDE15/10675146/CANBIO ), Luxembourg Institute of Health (LECR 20170540 ), “Fondation Cancer”, Luxembourg FC/2018/06 ; Kriibskrank Kanner Foundation, Janssen Cilag 2018 and Action LIONS Vaincre le Cancer, Luxembourg.
Publisher Copyright:
© 2019 The Author(s)
PY - 2019/8/28
Y1 - 2019/8/28
N2 - Compared to traditional therapies, such as surgery, radio-chemotherapy, or targeted approaches, immunotherapies based on immune checkpoint blockers (ICBs)have revolutionized the treatment of cancer. Although ICBs have yielded long-lasting results and have improved patient survival, this success has been seriously challenged by clinical observations showing that only a small fraction of patients benefit from this revolutionary therapy and no benefit has been found in patients with highly aggressive tumors. Efforts are currently ongoing to identify factors that predict the response to ICB. Among the different predictive markers established so far, the expression levels of immune checkpoint genes have proven to be important biomarkers for informing treatment choices. Therefore, understanding the mechanisms involved in the regulation of immune checkpoints is a key element that will facilitate novel combination approaches and optimize patient outcome. In this review, we discuss the impact of hypoxia and tumor cell plasticity on immune checkpoint gene expression and provide insight into the therapeutic value of the EMT signature and the rationale for novel combination approaches to improve ICB therapy and maximize the benefits for patients with cancer.
AB - Compared to traditional therapies, such as surgery, radio-chemotherapy, or targeted approaches, immunotherapies based on immune checkpoint blockers (ICBs)have revolutionized the treatment of cancer. Although ICBs have yielded long-lasting results and have improved patient survival, this success has been seriously challenged by clinical observations showing that only a small fraction of patients benefit from this revolutionary therapy and no benefit has been found in patients with highly aggressive tumors. Efforts are currently ongoing to identify factors that predict the response to ICB. Among the different predictive markers established so far, the expression levels of immune checkpoint genes have proven to be important biomarkers for informing treatment choices. Therefore, understanding the mechanisms involved in the regulation of immune checkpoints is a key element that will facilitate novel combination approaches and optimize patient outcome. In this review, we discuss the impact of hypoxia and tumor cell plasticity on immune checkpoint gene expression and provide insight into the therapeutic value of the EMT signature and the rationale for novel combination approaches to improve ICB therapy and maximize the benefits for patients with cancer.
KW - Cancer immunotherapy
KW - Epithelial-to-mesenchymal transition
KW - HIF
KW - Immune checkpoint blockers
KW - Immune suppression
KW - PD-L1 and CD47
UR - http://www.scopus.com/inward/record.url?scp=85066249277&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/31136782
U2 - 10.1016/j.canlet.2019.05.021
DO - 10.1016/j.canlet.2019.05.021
M3 - Review article
C2 - 31136782
AN - SCOPUS:85066249277
SN - 0304-3835
VL - 458
SP - 13
EP - 20
JO - Cancer Letters
JF - Cancer Letters
ER -