胰腺導管腺癌,，或稱PDA,，是致死性特別高的一種癌癥。但是一項新的研究顯示,，一種綜合性的化療以及一種可激活CD40 蛋白的藥物可在某個病人亞組和小鼠中有效地令腫瘤縮小,。 Gregory Beatty及其同事報告了一個臨床試驗的結果，在該試驗中，有少數(shù)的罹患無法由手術治愈的PDA病人可得益于這種CD40免疫療法,。研究人員接著分析了在以遺傳工程方法制造出來的罹患PDA的小鼠中的治療結果并發(fā)現(xiàn),，該嚙齒動物的一個亞組也對治療有良好的反應。 雖然CD40已知可促進T細胞功能并逆轉(zhuǎn)癌癥對免疫系統(tǒng)功能的抑制,，但研究人員還是驚訝地發(fā)現(xiàn),，由這一CD40 免疫療法所帶來的抗腫瘤效應與巨噬細胞有關。 據(jù)研究人員披露,，由CD40 所激活的巨噬細胞會迅速地滲入腫瘤之中并促使腫瘤基質(zhì)的損耗。 鑒于他們的發(fā)現(xiàn),，Beatty及其同事提示,，治療誘導的T細胞并非是讓免疫系統(tǒng)能夠?qū)拱┘毎匦璧摹?他們得出結論：以CD40 激活巨噬細胞可能給人們提供了一種在PDA中快速啟動抗腫瘤免疫的手段。 （生物谷Bioon.com）
生物谷推薦原文出處：
Science DOI: 10.1126/science.1198443
CD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans
Gregory L. Beatty1,2,6, Elena G. Chiorean3, Matthew P. Fishman1, Babak Saboury5, Ursina R. Teitelbaum2,6, Weijing Sun2,6, Richard D. Huhn4, Wenru Song4, Dongguang Li4, Leslie L. Sharp4, Drew A. Torigian2,5, Peter J. O’Dwyer2,6, and Robert H. Vonderheide1,2,6,*
Abstract
Immunosuppressive tumor microenvironments can restrain antitumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA). Because CD40 activation can reverse immune suppression and drive antitumor T cell responses, we tested the combination of an agonist CD40 antibody with gemcitabine chemotherapy in a small cohort of patients with surgically incurable PDA and observed tumor regressions in some patients. We reproduced this treatment effect in a genetically engineered mouse model of PDA and found unexpectedly that tumor regression required macrophages but not T cells or gemcitabine. CD40-activated macrophages rapidly infiltrated tumors, became tumoricidal, and facilitated the depletion of tumor stroma. Thus, cancer immune surveillance does not necessarily depend on therapy-induced T cells; rather, our findings demonstrate a CD40-dependent mechanism for targeting tumor stroma in the treatment of cancer.
