Tumor-induced perturbations of cytokines and immune cell networks.
Until recently, the intrinsically high level of cross-talk between immune cells, the complexity of immune cell development, and the pleiotropic nature of cytokine signaling have hampered progress in understanding the mechanisms of immunosuppression by which tumor cells circumvent native and adaptive immune responses. One technology that has helped to shed light on this complex signaling network is the cytokine antibody array, which facilitates simultaneous screening of dozens to hundreds of secreted signal proteins in complex biological samples. The combined applications of traditional methods of molecular and cell biology with the high-content, high-throughput screening capabilities of cytokine antibody arrays and other multiplexed immunoassays have revealed a complex mechanism that involves multiple cytokine signals contributed not just by tumor cells but by stromal cells and a wide spectrum of immune cell types. This review will summarize the interactions among cancerous and immune cell types, as well as the key cytokine signals that are required for tumors to survive immunoediting in a dormant state or to grow and spread by escaping it. Additionally, it will present examples of how probing secreted cell-cell signal networks in the tumor microenvironment (TME) with cytokine screens have contributed to our current understanding of these processes and discuss the implications of this understanding to antitumor therapies.
RayBiotech, Inc., 3607 Parkway Lane, Suite 100, Norcross, GA 30092, USA.
Brett
B
Burkholder
RayBiotech, Inc., Guangzhou 510600, China.
Ren-Yu
RY
Huang
RayBiotech, Inc., 3607 Parkway Lane, Suite 100, Norcross, GA 30092, USA.
Rob
R
Burgess
RayBiotech, Inc., 3607 Parkway Lane, Suite 100, Norcross, GA 30092, USA; RayBiotech, Inc., Guangzhou 510600, China.
Shuhong
S
Luo
RayBiotech, Inc., 3607 Parkway Lane, Suite 100, Norcross, GA 30092, USA.
Valerie Sloane
VS
Jones
RayBiotech, Inc., Guangzhou 510600, China.
Wenji
W
Zhang
RayBiotech, Inc., Guangzhou 510600, China.
Zhi-Qiang
ZQ
Lv
RayBiotech, Inc., Guangzhou 510600, China.
Chang-Yu
CY
Gao
RayBiotech, Inc., Guangzhou 510600, China.
Bao-Ling
BL
Wang
RayBiotech, Inc., Guangzhou 510600, China.
Yu-Ming
YM
Zhang
RayBiotech, Inc., 3607 Parkway Lane, Suite 100, Norcross, GA 30092, USA; RayBiotech, Inc., Guangzhou 510600, China; South China Biochip Research Center, Guangzhou 510630, China. Electronic address: rhuang@raybiotech.com.
Ruo-Pan
RP
Huang
D002450:Cell Communication / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000378:metabolism*; D007165:Immunosuppression Therapy; D015166:Monitoring, Immunologic; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology
D016207:Cytokines
Cancer; Cytokine; Immunosuppression; Immunosurveillance