The tumor microenvironment and its role in promoting tumor growth

被引:0
作者
T L Whiteside
机构
[1] Professor of Pathology,
[2] Immunology and Otolaryngology,undefined
[3] University of Pittsburgh School of Medicine and The Hillman Cancer Center,undefined
来源
Oncogene | 2008年 / 27卷
关键词
chronic inflammation; human tumors; immune suppression; tumor escape;
D O I
暂无
中图分类号
学科分类号
摘要
The tumor microenvironment is created by the tumor and dominated by tumor-induced interactions. Although various immune effector cells are recruited to the tumor site, their anti-tumor functions are downregulated, largely in response to tumor-derived signals. Infiltrates of inflammatory cells present in human tumors are chronic in nature and are enriched in regulatory T cells (Treg) as well as myeloid suppressor cells (MSC). Immune cells in the tumor microenvironment not only fail to exercise antitumor effector functions, but they are co-opted to promote tumor growth. Sustained activation of the NF-κB pathway in the tumor milieu represents one mechanism that appears to favor tumor survival and drive abortive activation of immune cells. The result is tumor escape from the host immune system. Tumor escape is accomplished through the activation of one or several molecular mechanisms that lead to inhibition of immune cell functions or to apoptosis of anti-tumor effector cells. The ability to block tumor escape depends on a better understanding of cellular and molecular pathways operating in the tumor microenvironment. Novel therapeutic strategies that emerge are designed to change the pro-tumor microenvironment to one favoring acute responses and potent anti-tumor activity.
引用
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页码:5904 / 5912
页数:8
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[1]  
Albers AE(2002)Immune responses to p53 in patients with cancer: enrichment in tetramer+p53 peptide-specific T cells and regulatory CD4+CD25+ cells at tumor sites Cancer Immunol Immunother 62 670-679
[2]  
Kim G(2004)Posttraumatic inflammation is a complex response based on the pathological expression of the nervous, immune and endocrine function systems Exp Biol Med 229 170-181
[3]  
Ferris RL(2001)Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer J Immunol 166 678-689
[4]  
Chikamatsu K(2000)Clinical significance of defective dendritic cell differentiation in cancer Clin Cancer Res 6 1755-1766
[5]  
DeLeo AB(2007)Role of regulatory T cells and FOXP3 in human diseases J Allergy Clin Immunol 120 227-235
[6]  
Whiteside TL(2004)Cancer: an inflammatory link Nature 431 405-406
[7]  
Aller MA(2001)Inflammation and cancer: back to Virchow? Lancet 357 539-545
[8]  
Arias JL(2006)Expansion of FOXP3 high regulatory T cells by human dendritic cells (DCs) Blood 108 2655-2661
[9]  
Nava MP(1994) and after injection of cytokine-matured DCs in myeloma patients Cancer 74 1275-1282
[10]  
Arias J(2007)Tumor specific cytolysis by tumor infiltrating lymphocytes in breast cancer Cancer Res 67 8865-8873