enhancement of anti-tumor immunity in dendritic cell therapy toward gynecological malignancies

增强树突状细胞治疗妇科恶性肿瘤的抗肿瘤免疫力

• 批准号: 17591732
• 负责人: MANDAI Masaki
• 金额: $ 1.92万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591732/
• 关键词: gynecologic cancer; tumor immunity; PD-L1; CD8+ T cell; K-562; 卵巣癌; PD-L1; 血管内皮前駆細胞; 免疫療法

Recent development in treatment modalities has achieved a marked improvement in the short-term survival of patients with ovarian cancer. Nevertheless, the long-term prognosis in advanced cases remains unsatisfactory, requiring a new paradigm in the treatment strategy. Various prognostic factors have been proposed and used clinically to predict the clinical course and to aid clinical decision-making in ovarian cancer patients. However, even using this system, prediction of the long-term prognosis, especially of late recurrence after remission remains difficult, suggesting a need to introduce other parameters such as sensitivity to chemotherapy and the strength of anti-tumor immune response. Several reports have shown the significance of tumor-infiltrating lymphocytes (TILs) as a prognostic factor in malignant tumors such as cutaneous melanoma, colorectal cancer, esophageal cancer, renal cancer, and ovarian cancer, suggesting that immunological parameters are significant and useful in as … More sessing the prognosis of cancer patients. However, there are few reports suggesting that a specific molecule can represent the strength of the host-tumor immunity. Therefore, in this project, we firstly analyzed if some of these immunological parameters are really related to the prognosis of the patient, and found that CD8+T cell number in the tumor as well as PD-L1 expression (ovarian cancer), or COX-2 expression (cervical adenocarcinoma) correlated with patient prognosis, indicating that tumor immunity is indeed important. Then, we tried to establish a method to acquire efficient tumor immunity toward ovarian cancer. Human dendiritic cells were collected from ovarian cancer patient blood with informed consent and anti-tumor immunity toward autologus ovarian cancer was measured in various conditions. Anti-tumor immunity was enhanced when DCs were co-cultured with K-562 cells transfected with and overexpressed Flt-3, suggesting that immunostimulatory signal from bystander cells can enhance tumor immunity. We are now preparing a mouse in vivo model of immunotherapy to deliver immunostimulatory signal using non-immune cell Less

最近在治疗方式上的发展已经实现了卵巢癌患者短期存活率的显著改善。然而，晚期病例的长期预后仍然不令人满意，需要在治疗策略上采取新的范例。各种预后因素已经被提出并用于临床，以预测卵巢癌患者的临床病程，并辅助临床决策。然而，即使使用该系统，预测长期预后，特别是缓解后的晚期复发仍然困难，提示需要引入其他参数，如对化疗的敏感性和抗肿瘤免疫反应的强度。一些报告表明，肿瘤浸润性淋巴细胞(TIL)在皮肤黑色素瘤、结直肠癌、食道癌、肾癌和卵巢癌等恶性肿瘤中作为预后因子具有重要意义，提示免疫学参数在AS…中是重要和有用的。更有利于癌症患者的预后。然而，很少有报道表明一个特定的分子可以代表宿主-肿瘤免疫的强度。因此，在这个项目中，我们首先分析了其中一些免疫学参数是否真的与患者的预后有关，发现肿瘤中CD8+T细胞的数量以及PD-L1的表达(卵巢癌)或COX-2的表达(宫颈癌)与患者的预后相关，表明肿瘤免疫确实很重要。然后，我们试图建立一种获得对卵巢癌有效的肿瘤免疫的方法。在知情同意的情况下，采集卵巢癌患者外周血中的人趋化因子细胞，并在不同条件下检测其抗肿瘤免疫功能。DC与高表达Flt-3的K-562细胞共培养后，抗肿瘤免疫功能增强，提示旁观者细胞的免疫刺激信号可增强肿瘤免疫功能。我们现在正在准备一种免疫治疗的小鼠体内模型，以使用较少的非免疫细胞传递免疫刺激信号

项目成果

Immortalized ovarian surface epithelial cells acquire tumorigenicity by Acrogranin gene overexpression.

• DOI: 10.3892/or.17.2.329
• 发表时间: 2007-02
• 期刊: Oncology reports
• 影响因子: 4.2
• 作者: Masanori Miyanishi;M. Mandai;N. Matsumura;K. Yamaguchi;J. Hamanishi;T. Higuchi;K. Takakura;S. Fujii-S

Increased cyclooxygenase-2 expression is correlated with suppressed anti-tumor immunity in cervical adenocarcinoma.

环氧合酶-2 表达增加与宫颈腺癌中抗肿瘤免疫抑制相关。

• 期刊: Int.Journal of Gynecologiccal Cancer (in press)
• 作者: Chen-T.H;Fukuhara-K;Mandai-M
• 通讯作者: Mandai-M

Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer

• DOI: 10.1073/pnas.0611533104
• 发表时间: 2007-02-27
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Hamanishi, Junzo;Mandai, Masaki;Fujii, Shingo
• 通讯作者: Fujii, Shingo

LH/hCG action and development of ovarian cancer - A short review on biological and clinical/epidemiological aspects

• DOI: 10.1016/j.mce.2006.11.014
• 发表时间: 2007-04-15
• 期刊: MOLECULAR AND CELLULAR ENDOCRINOLOGY
• 影响因子: 4.1
• 作者: Mandai, Masaki;Konishi, Ikuo;Fujii, Shingo
• 通讯作者: Fujii, Shingo

Increased cyclooxygenase-2 expression is correlated with suppressed antitumor immunity in cervical adenocarcinomas

• DOI: 10.1111/j.1525-1438.2006.00385.x
• 发表时间: 2006-03-01
• 期刊: INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
• 影响因子: 4.8
• 作者: Chen, TH;Fukuhara, K;Fujii, S
• 通讯作者: Fujii, S