6月6日，Cancer Research在線報道，腫瘤細胞中DNA應激和p53狀態(tài)可差異性影響TOLL樣受體固有免疫家族的表達,。
轉錄因子p53調節(jié)包括TOLL樣受體（TLR）在內的固有免疫相關基因的表達,。這提示p53也調節(jié)人類免疫反應,。TLR家族構成識別病原相關的分子模式(PAMPs)的細胞膜糖蛋白,，介導固有免疫反應,。TLR激動劑已被用于腫瘤治療的佐劑,。
研究證實，阿霉素,、5氟尿嘧啶,、紫外線以及電離輻射均可以細胞系和損傷特異性的方式引起TLR表達的改變,。特別是，治療誘導的TLR表達改變可造成其下游細胞因子對相應配體刺激的反應性表達上升,。刺激TLR表達的DNA應激壓力效應主要由p53介導。P53的幾個癌相關突變顯著改變TLR基因表達,。在所有檢測過的細胞系中，TLR3的誘導表達是p53依賴性的,，而TLR9則較少依賴p53的狀態(tài),。此外,，所檢測的10個固有免疫TLR基因家族成員的可誘導性呈現(xiàn)差異性。
這些發(fā)現(xiàn)證實,，基于TLR的腫瘤治療所應該考慮到p53狀態(tài),、染色體應激和每類TLR分子的反應性等背景因素。（生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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The human TLR innate immune gene family is differentially influenced by DNA stress and p53 status in cancer cells
Maria Shatz1, Daniel Menendez2, and Michael A Resnick3,*
The transcription factor p53 regulates genes associated with a wide range of functions, including the Toll-like receptor (TLR) set of innate immunity genes, suggesting that p53 also modulates the human immune response. The TLR family comprises membrane glycoproteins that recognize pathogen-associated molecular patterns (PAMPs) and mediate innate immune responses, and TLR agonists are being used as adjuvants in cancer treatments. Here, we demonstrate that doxorubicin, 5-fluorouracil, and UV and ionizing radiation elicit changes in TLR expression that are cell line- and damage-specific. Specifically, treatment-induced expression changes led to increased downstream cytokine expression in response to ligand stimulation. The effect of DNA stressors on TLR expression was mainly mediated by p53, and several p53 cancer-associated mutants dramatically altered the pattern of TLR gene expression. In all cell lines tested, TLR3 induction was p53-dependent, while induction of TLR9, the most stress-responsive family member, was less dependent on status of p53. In addition, each of the 10 members of the innate immune TLR gene family tested was differentially inducible. Our findings therefore demonstrate that the matrix of p53 status, chromosome stress, and responsiveness of individual TLRs should be considered in TLR-based cancer therapies.
