TY - JOUR
T1 - Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments
AU - Kryczek, Ilona
AU - Banerjee, Mousumi
AU - Cheng, Pui
AU - Vatan, Linhua
AU - Szeliga, Wojciech
AU - Wei, Shuang
AU - Huang, Emina
AU - Finlayson, Emily
AU - Simeone, Diane
AU - Welling, Theodore H.
AU - Chang, Alfred
AU - Coukos, George
AU - Liu, Rebecca
AU - Zou, Weiping
PY - 2009
Y1 - 2009
N2 - Th17 cells play an active role in autoimmune diseases. However, the nature of Th17 cells is poorly understood in cancer patients.We studied Th17 cells, the associated mechanisms, and clinical significance in 201 ovarian cancer patients. Tumor-infiltrating Th17 cells exhibit a polyfunctional effector T-cell phenotype, are positively associated with effector cells, and are negatively associated with tumor-infiltrating regulatory T cells. Tumor-associated macrophages promote Th17 cells through interleukin-1β (IL-1β), whereas tumor-infiltrating regulatory T cells inhibit Th17 cells through an adenosinergic pathway. Furthermore, through synergistic action between IL-17 and interferon-γ, Th17 cells stimulate CXCL9 and CXCL10 production to recruit effector T cells to the tumor microenvironment. The levels of CXCL9 and CXCL10 are associated with tumor-infiltrating effector T cells. The levels of tumor-infiltrating Th17 cells and the levels of ascites IL-17 are reduced in more advanced diseases and positively predict patient outcome. Altogether, Th17 cells may contribute to protective human tumor immunity through inducing Th1-type chemokines and recruiting effector cells to the tumor microenvironment. Inhibition of Th17 cells represents a novel immune evasion mechanism. This study thus provides scientific and clinical rationale for developing novel immuneboosting strategies based on promoting the Th17 cell population in cancer patients.
AB - Th17 cells play an active role in autoimmune diseases. However, the nature of Th17 cells is poorly understood in cancer patients.We studied Th17 cells, the associated mechanisms, and clinical significance in 201 ovarian cancer patients. Tumor-infiltrating Th17 cells exhibit a polyfunctional effector T-cell phenotype, are positively associated with effector cells, and are negatively associated with tumor-infiltrating regulatory T cells. Tumor-associated macrophages promote Th17 cells through interleukin-1β (IL-1β), whereas tumor-infiltrating regulatory T cells inhibit Th17 cells through an adenosinergic pathway. Furthermore, through synergistic action between IL-17 and interferon-γ, Th17 cells stimulate CXCL9 and CXCL10 production to recruit effector T cells to the tumor microenvironment. The levels of CXCL9 and CXCL10 are associated with tumor-infiltrating effector T cells. The levels of tumor-infiltrating Th17 cells and the levels of ascites IL-17 are reduced in more advanced diseases and positively predict patient outcome. Altogether, Th17 cells may contribute to protective human tumor immunity through inducing Th1-type chemokines and recruiting effector cells to the tumor microenvironment. Inhibition of Th17 cells represents a novel immune evasion mechanism. This study thus provides scientific and clinical rationale for developing novel immuneboosting strategies based on promoting the Th17 cell population in cancer patients.
UR - http://www.scopus.com/inward/record.url?scp=69849107597&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=69849107597&partnerID=8YFLogxK
U2 - 10.1182/blood-2009-03-208249
DO - 10.1182/blood-2009-03-208249
M3 - Article
C2 - 19470694
AN - SCOPUS:69849107597
SN - 0006-4971
VL - 114
SP - 1141
EP - 1149
JO - Blood
JF - Blood
IS - 6
ER -