8月31日,，Cancer Research 雜志電,，自噬抑制常規(guī)化療的療效,，但其對(duì)免疫的影響研究甚少,。本研究發(fā)現(xiàn),，化療使腫瘤細(xì)胞更容易被體內(nèi)的細(xì)胞毒性T細(xì)胞（CTL）所溶解。此外,，不表達(dá)抗原的旁觀者腫瘤細(xì)胞同樣被CTL殺死,。這種效果，是腫瘤細(xì)胞表面的甘露糖-6 - 磷酸受體（MPR）短暫卻顯著的表達(dá)上調(diào)所介導(dǎo)的,。
綜合治療方法的抗腫瘤效果與MPR上調(diào)密切相關(guān),。阻斷這種上調(diào)將削弱免疫治療和化療的綜合治療效應(yīng)。在進(jìn)行化療的,，多種小鼠腫瘤模型和多發(fā)性骨髓瘤患者中,，研究者均觀察到MPR在腫瘤細(xì)胞表面的積累。值得一提的是,，化療誘導(dǎo)的自噬作用是導(dǎo)致這種受體再分配的原因,。
總之，本研究結(jié)果揭示了一個(gè)傳統(tǒng)的癌癥化療和免疫治療的抗腫瘤作用的分子機(jī)制,。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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Autophagy induced by conventional chemotherapy mediates tumor cell sensitivity to immunotherapy
Rupal Ramakrishnan1, Chun huang2, Hyun-Il Cho1, Mark Lloyd3, Joseph Johnson4, Xiubao Ren5, Soner Altiok6, Daniel Sullivan7, Jeffrey Weber8, Esteban Celis9, and Dmitry I. Gabrilovich1,*
Autophagy attenuates the efficacy of conventional chemotherapy but its effects on immunotherapy have been little studied. Here we report that chemotherapy renders tumor cells more susceptible to lysis by cytotoxic T cells (CTL) in vivo. Moreover, bystander tumor cells that did not express antigen were killed by CTL. This effect was mediated by transient but dramatic upregulation of the mannose-6-phosphate receptor (MPR) on the tumor cell surface. Antitumor effects of combined treatment related to the kinetics of MPR upregulation and abrogation of this event abolished the combined effect of immunotherapy and chemotherapy. MPR accumulation on the tumor cell surface during chemotherapy was observed in different mouse tumor models and in patients with multiple myeloma. Notably, this effect was the result of redistribution of the receptor caused by chemotherapy-inducible autophagy. Together, our findings reveal one molecular mechanism through which the antitumor effects of conventional cancer chemotherapy and immunotherapy are realized.
