TY - JOUR
T1 - Critical role of tumor microenvironment in shaping NK cell functions
T2 - Implication of hypoxic stress
AU - Hasmim, Meriem
AU - Messai, Yosra
AU - Ziani, Linda
AU - Thiery, Jerome
AU - Bouhris, Jean Henri
AU - Noman, Muhammad Zaeem
AU - Chouaib, Salem
N1 - Publisher Copyright:
© 2015 Hasmim, Messai, Ziani, Thiery, Bouhris, Noman and Chouaib.
PY - 2015
Y1 - 2015
N2 - Blurring the boundary between innate and adaptive immune system, natural killer (NK) cells, a key component of the innate immunity, are recognized as potent anticancer mediators. Extensive studies have been detailed on how NK cells get activated and recognize cancer cells. In contrast, few studies have been focused on how tumor microenvironment-mediated immunosubversion and immunoselection of tumor-resistant variants may impair NK cell function. Accumulating evidences indicate that several cell subsets (macrophages, myeloid-derived suppressive cells, T regulatory cells, dendritic cells, cancer-associated fibroblasts, and tumor cells), their secreted factors, as well as metabolic components (i.e., hypoxia) have immunosuppressive roles in the tumor microenvironment and are able to condition NK cells to become anergic. In this review, we will describe how NK cells react with different stromal cells in the tumor microenvironment. This will be followed by a discussion on the role of hypoxic stress in the regulation of NK cell functions. The aim of this review is to provide a better understanding of how the tumor microenvironment impairs NK cell functions, thereby limiting the use of NK cell-based therapy, and we will attempt to suggest more efficient tools to establish a more favorable tumor microenvironment to boost NK cell cytotoxicity and control tumor progression.
AB - Blurring the boundary between innate and adaptive immune system, natural killer (NK) cells, a key component of the innate immunity, are recognized as potent anticancer mediators. Extensive studies have been detailed on how NK cells get activated and recognize cancer cells. In contrast, few studies have been focused on how tumor microenvironment-mediated immunosubversion and immunoselection of tumor-resistant variants may impair NK cell function. Accumulating evidences indicate that several cell subsets (macrophages, myeloid-derived suppressive cells, T regulatory cells, dendritic cells, cancer-associated fibroblasts, and tumor cells), their secreted factors, as well as metabolic components (i.e., hypoxia) have immunosuppressive roles in the tumor microenvironment and are able to condition NK cells to become anergic. In this review, we will describe how NK cells react with different stromal cells in the tumor microenvironment. This will be followed by a discussion on the role of hypoxic stress in the regulation of NK cell functions. The aim of this review is to provide a better understanding of how the tumor microenvironment impairs NK cell functions, thereby limiting the use of NK cell-based therapy, and we will attempt to suggest more efficient tools to establish a more favorable tumor microenvironment to boost NK cell cytotoxicity and control tumor progression.
KW - HIF
KW - Immune suppression
KW - Microenvironment
KW - Natural killer cells
KW - Solid tumors
UR - http://www.scopus.com/inward/record.url?scp=84946552670&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2015.00482
DO - 10.3389/fimmu.2015.00482
M3 - Review article
AN - SCOPUS:84946552670
SN - 1664-3224
VL - 6
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - SEP
M1 - 482
ER -