Dendritic cell immunotherapy combined with gemcitabine chemotherapy enhances survival in a murine model of pancreatic carcinoma.
Dendritic cell immunotherapy combined with gemcitabine chemotherapy enhances survival in a murine model of pancreatic carcinoma.
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DOI：
10.1007/s00262-013-1407-9
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发表时间：
2013-06
影响因子：
5.8
通讯作者：
Pilon-Thomas, Shari
中科院分区：
文献类型：
--
作者：
Ghansah, Tomar;Vohra, Nasreen;Kinney, Kathleen;Weber, Amy;Kodumudi, Krithika;Springett, Gregory;Sarnaik, Amod A.;Pilon-Thomas, Shari
关键词：
胰腺癌是一种侵袭性极强的恶性肿瘤，预后极差。癌症患者和荷瘤小鼠具有多种免疫调节亚群，包括调节性T细胞（TCFs）和髓源性抑制细胞（MDSC），这可能限制胰腺癌抗肿瘤免疫疗法的有效性。调节这些亚群可能会增强抗肿瘤免疫力。本研究的目的是探索在胰腺癌小鼠模型中去除免疫调节细胞以增强基于树突状细胞（DC）的癌症免疫治疗。流式细胞术结果显示，与对照组相比，未治疗的胰腺癌荷瘤小鼠中TdR和MDSC均增加。单独或与基于DC的疫苗接种组合消除TdR对胰腺肿瘤生长或存活没有影响。吉西他滨（Gem）是一种常规用于治疗胰腺癌患者的化疗药物。Gem治疗导致荷瘤小鼠脾脏中MDSC百分比显著降低，但未提高总生存率。然而，与DC疫苗接种随后Gem治疗的组合疗法导致肿瘤生长的显著延迟和携带胰腺癌的小鼠的存活率的提高。在胰腺癌患者的外周血中测量到增加的MDSC。Gem治疗还导致胰腺癌患者中这一人群的减少，这表明基于DC的癌症疫苗接种和Gem的联合治疗可能会改善胰腺癌患者的治疗。
Pancreatic cancer is an extremely aggressive malignancy with a dismal prognosis. Cancer patients and tumor-bearing mice have multiple immunoregulatory subsets including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC) that may limit the effectiveness of anti-tumor immunotherapies for pancreatic cancer. It is possible that modulating these subsets will enhance anti-tumor immunity. The goal of this study was to explore depletion of immunoregulatory cells to enhance dendritic cell (DC)-based cancer immunotherapy in a murine model of pancreatic cancer. Flow cytometry results showed an increase in both Tregs and MDSC in untreated pancreatic cancer-bearing mice compared to control. Elimination of Tregs alone or in combination with DC-based vaccination had no effect on pancreatic tumor growth or survival. Gemcitabine (Gem) is a chemotherapeutic drug routinely used for the treatment of pancreatic cancer patients. Treatment with Gem led to a significant decrease in MDSC percentages in the spleens of tumor-bearing mice but did not enhance overall survival. However, combination therapy with DC vaccination followed by Gem treatment led to a significant delay in tumor growth and improved survival in pancreatic cancer-bearing mice. Increased MDSC were measured in the peripheral blood of patients with pancreatic cancer. Treatment with Gem also led to a decrease of this population in pancreatic patients suggesting that combination therapy with DC-based cancer vaccination and Gem may lead to improved treatments for patients with pancreatic cancer.
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影响因子：
24.5
作者：
Bauer, C.;Bauernfeind, F.;Dauer, M.
通讯作者：
Dauer, M.
DOI：
10.1016/j.jamcollsurg.2004.01.008
发表时间：
2004-05-01
影响因子：
5.2
作者：
Cleary, SP;Gryfe, R;Gallinger, S
通讯作者：
Gallinger, S
DOI：
10.1158/1078-0432.ccr-09-3272
发表时间：
2010-03-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Nagaraj S;Youn JI;Weber H;Iclozan C;Lu L;Cotter MJ;Meyer C;Becerra CR;Fishman M;Antonia S;Sporn MB;Liby KT;Rawal B;Lee JH;Gabrilovich DI
通讯作者：
Gabrilovich DI
影响因子：
9
作者：
Hernandez, Jonathan;Mullinax, John;Rosemurgy, Alexander
通讯作者：
Rosemurgy, Alexander
影响因子：
2.9
作者：
Fukunaga, A;Miyamoto, M;Katoh, H
通讯作者：
Katoh, H