TY - JOUR
T1 - Improving cancer immunotherapy by targeting the hypoxic tumor microenvironment
T2 - New opportunities and challenges
AU - Noman, Muhammad Zaeem
AU - Hasmim, Meriem
AU - Lequeux, Audrey
AU - Xiao, Malina
AU - Duhem, Caroline
AU - Chouaib, Salem
AU - Berchem, Guy
AU - Janji, Bassam
N1 - Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/9
Y1 - 2019/9
N2 - Initially believed to be a disease of deregulated cellular and genetic expression, cancer is now also considered a disease of the tumor microenvironment. Over the past two decades, significant and rapid progress has been made to understand the complexity of the tumor microenvironment and its contribution to shaping the response to various anti-cancer therapies, including immunotherapy. Nevertheless, it has become clear that the tumor microenvironment is one of the main hallmarks of cancer. Therefore, a major challenge is to identify key druggable factors and pathways in the tumor microenvironment that can be manipulated to improve the efficacy of current cancer therapies. Among the different tumor microenvironmental factors, this review will focus on hypoxia as a key process that evolved in the tumor microenvironment. We will briefly describe our current understanding of the molecular mechanisms by which hypoxia negatively affects tumor immunity and shapes the anti-tumor immune response. We believe that such understanding will provide insight into the therapeutic value of targeting hypoxia and assist in the design of innovative combination approaches to improve the efficacy of current cancer therapies, including immunotherapy.
AB - Initially believed to be a disease of deregulated cellular and genetic expression, cancer is now also considered a disease of the tumor microenvironment. Over the past two decades, significant and rapid progress has been made to understand the complexity of the tumor microenvironment and its contribution to shaping the response to various anti-cancer therapies, including immunotherapy. Nevertheless, it has become clear that the tumor microenvironment is one of the main hallmarks of cancer. Therefore, a major challenge is to identify key druggable factors and pathways in the tumor microenvironment that can be manipulated to improve the efficacy of current cancer therapies. Among the different tumor microenvironmental factors, this review will focus on hypoxia as a key process that evolved in the tumor microenvironment. We will briefly describe our current understanding of the molecular mechanisms by which hypoxia negatively affects tumor immunity and shapes the anti-tumor immune response. We believe that such understanding will provide insight into the therapeutic value of targeting hypoxia and assist in the design of innovative combination approaches to improve the efficacy of current cancer therapies, including immunotherapy.
KW - Autophagy
KW - HIF
KW - Hypoxia
KW - Immune checkpoints
KW - Immunotherapy
KW - Tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85077470251&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/31540045
U2 - 10.3390/cells8091083
DO - 10.3390/cells8091083
M3 - Review article
C2 - 31540045
AN - SCOPUS:85077470251
SN - 2073-4409
VL - 8
JO - Cells
JF - Cells
IS - 9
M1 - 1083
ER -