【进展|热点】Science:胰腺腺癌治疗新思路-CD40分子激活抗肿瘤细胞

Science. 2011 Mar 25;331(6024):1612-6.
CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans.
Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, Huhn RD, Song W, Li D, Sharp LL, Torigian DA, [url=http://www.ncbi.nlm.nih.gov/pubmed?term=%22O'Dwyer%20PJ%22%5BAuthor%5D]O'Dwyer PJ[/url],Vonderheide RH.
Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
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.

内容简介：
以往，胰腺导管腺癌患者预后欠佳，常在确诊后数月内死亡。但最近，来自费城宾夕法尼亚大学Abramson癌症中心的免疫学家Robert Vonderheide和他的团队通过研究发现，CD40激活的抗肿瘤T细胞可发挥杀伤胰腺导管腺癌作用，这一结论已在人体和大鼠体内均得以验证，从而为胰腺癌治疗提供新思路。