Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment

H Yu, M Kortylewski, D Pardoll - Nature reviews immunology, 2007 - nature.com
Nature reviews immunology, 2007nature.com
Immune cells in the tumour microenvironment not only fail to mount an effective anti-tumour
immune response, but also interact intimately with the transformed cells to promote
oncogenesis actively. Signal transducer and activator of transcription 3 (STAT3), which is a
point of convergence for numerous oncogenic signalling pathways, is constitutively activated
both in tumour cells and in immune cells in the tumour microenvironment. Constitutively
activated STAT3 inhibits the expression of mediators necessary for immune activation …
Abstract
Immune cells in the tumour microenvironment not only fail to mount an effective anti-tumour immune response, but also interact intimately with the transformed cells to promote oncogenesis actively. Signal transducer and activator of transcription 3 (STAT3), which is a point of convergence for numerous oncogenic signalling pathways, is constitutively activated both in tumour cells and in immune cells in the tumour microenvironment. Constitutively activated STAT3 inhibits the expression of mediators necessary for immune activation against tumour cells. Furthermore, STAT3 activity promotes the production of immunosuppressive factors that activate STAT3 in diverse immune-cell subsets, altering gene-expression programmes and, thereby, restraining anti-tumour immune responses. As such, STAT3 propagates several levels of crosstalk between tumour cells and their immunological microenvironment, leading to tumour-induced immunosuppression. Consequently, STAT3 has emerged as a promising target for cancer immunotherapy.
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