2012年8月31日 訊 /生物谷BIOON/ --發(fā)表在Journal of Leukocyte Biology雜志上的一項(xiàng)最新研究表明單核細(xì)胞來(lái)源的樹(shù)突狀細(xì)胞誘導(dǎo)免疫反應(yīng)來(lái)抗擊腫瘤并非如預(yù)期的那樣有效,。
刊登在2012年9月Journal of Leukocyte Biology雜志上的一則研究報(bào)告解釋了為什么有些癌癥疫苗沒(méi)有達(dá)到預(yù)期的效果，同時(shí)發(fā)現(xiàn)了一種治療自身免疫問(wèn)題的新策略,。在該報(bào)告中,，科學(xué)家證實(shí)即使癌癥在早期階段，樹(shù)突狀細(xì)胞會(huì)產(chǎn)生一種負(fù)向免疫應(yīng)答,，以防止淋巴細(xì)胞抵抗腫瘤,。雖然用于癌癥治療，這些有缺陷的樹(shù)突狀細(xì)胞用于防止免疫系統(tǒng)受到下列情況的攻擊如自身免疫性疾病,、器官移植等可能是有價(jià)值的治療工具,。
巴西圣保羅大學(xué)腫瘤免疫學(xué)實(shí)驗(yàn)室José Alexandre M. Barbuto博士表示：癌癥免疫治療一直是一個(gè)難以實(shí)現(xiàn)的目標(biāo)，雖然非常具有有前途,，但似乎從來(lái)沒(méi)有實(shí)現(xiàn)過(guò),。這項(xiàng)研究有助于我們更好地了解腫瘤逃避免疫識(shí)別的機(jī)制，便于我們?nèi)绾握嬲行У乩妹庖呦到y(tǒng)對(duì)抗腫瘤,。
在這項(xiàng)研究中,，研究人員獲得了一個(gè)小部分乳腺癌患者和健康志愿者的血液樣本。然后分離出血細(xì)胞并誘導(dǎo)成為樹(shù)突狀細(xì)胞,。研究人員使用這些實(shí)驗(yàn)室產(chǎn)生的樹(shù)突狀細(xì)胞誘導(dǎo)其他免疫系統(tǒng)細(xì)胞即淋巴細(xì)胞的免疫響應(yīng),。盡管從健康供體中誘導(dǎo)的樹(shù)突狀細(xì)胞能產(chǎn)生劇烈的淋巴細(xì)胞反應(yīng)，但從癌癥患者中得到的樹(shù)突狀細(xì)胞主要誘導(dǎo)一種特定類(lèi)型淋巴細(xì)胞的激活,，該類(lèi)型淋巴細(xì)胞充當(dāng)“剎車(chē)”監(jiān)管其他類(lèi)型淋巴細(xì)胞阻斷其活化,。本研究為研究調(diào)節(jié)啟動(dòng)抗腫瘤反應(yīng)所涉的一個(gè)關(guān)鍵免疫細(xì)胞類(lèi)型即樹(shù)突狀細(xì)胞的基本機(jī)制提供了新的見(jiàn)解。（生物谷：Bioon.com）
doi:10.1189/jlb.0112048
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Monocyte-derived dendritic cells from breast cancer patients are biased to induce CD4+CD25+Foxp3+ regulatory T cells
Rodrigo Nalio Ramos, Lilian Sally Chin, Ana Paula S. A. dos Santos, Patrícia Cruz Bergami-Santos, Fábio Laginha, and José Alexandre M. Barbuto.
DCs orchestrate immune responses contributing to the pattern of response developed. In cancer, DCs may play a dysfunctional role in the induction of CD4(+)CD25(+)Foxp3(+) Tregs, contributing to immune evasion. We show here that Mo-DCs from breast cancer patients show an altered phenotype and induce preferentially Tregs, a phenomenon that occurred regardless of DC maturation stimulus (sCD40L, cytokine cocktail, TNF-α, and LPS). The Mo-DCs of patients induced low proliferation of allogeneic CD3(+)CD25(neg)Foxp3(neg) cells, which after becoming CD25(+), suppressed mitogen-stimulated T cells. Contrastingly, Mo-DCs from healthy donors induced a stronger proliferative response, a low frequency of CD4(+)CD25(+)Foxp3(+) with no suppressive activity. Furthermore, healthy Mo-DCs induced higher levels of IFN-γ, whereas the Mo-DCs of patients induced higher levels of bioactive TGF-β1 and IL-10 in cocultures with allogeneic T cells. Interestingly, TGF-β1 blocking with mAb in cocultures was not enough to completely revert the Mo-DCs of patients' bias toward Treg induction. Altogether, these findings should be considered in immunotherapeutic approaches for cancer based on Mo-DCs.
