Impact of hypoxic tumor microenvironment and tumor cell plasticity on the expression of immune checkpoints

Audrey Lequeux; Muhammad Zaeem Noman; Malina Xiao; Delphine Sauvage; Kris Van Moer; Elodie Viry; Irene Bocci; Meriem Hasmim; Manon Bosseler; Guy Berchem; Bassam Janji

doi:10.1016/j.canlet.2019.05.021

Impact of hypoxic tumor microenvironment and tumor cell plasticity on the expression of immune checkpoints

Audrey Lequeux, Muhammad Zaeem Noman, Malina Xiao, Delphine Sauvage, Kris Van Moer, Elodie Viry, Irene Bocci, Meriem Hasmim, Manon Bosseler, Guy Berchem, Bassam Janji^*

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

65 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	13-20
Number of pages	8
Journal	Cancer Letters
Volume	458
DOIs	https://doi.org/10.1016/j.canlet.2019.05.021
Publication status	Published - 28 Aug 2019

Keywords

Cancer immunotherapy
Epithelial-to-mesenchymal transition
HIF
Immune checkpoint blockers
Immune suppression
PD-L1 and CD47

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10.1016/j.canlet.2019.05.021

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@article{305f2533957c4d5ca8e17b0187735b1d,

title = "Impact of hypoxic tumor microenvironment and tumor cell plasticity on the expression of immune checkpoints",

abstract = "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.",

keywords = "Cancer immunotherapy, Epithelial-to-mesenchymal transition, HIF, Immune checkpoint blockers, Immune suppression, PD-L1 and CD47",

author = "Audrey Lequeux and Noman, {Muhammad Zaeem} and Malina Xiao and Delphine Sauvage and {Van Moer}, Kris and Elodie Viry and Irene Bocci and Meriem Hasmim and Manon Bosseler and Guy Berchem and Bassam Janji",

note = "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: {\textcopyright} 2019 The Author(s)",

year = "2019",

month = aug,

day = "28",

doi = "10.1016/j.canlet.2019.05.021",

language = "English",

volume = "458",

pages = "13--20",

journal = "Cancer Letters",

issn = "0304-3835",

publisher = "Elsevier Ireland Ltd",

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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

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 -

Impact of hypoxic tumor microenvironment and tumor cell plasticity on the expression of immune checkpoints

Abstract

Keywords

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