Vaccination with embryonic stem cells protects against lung cancer: is a broad-spectrum prophylactic vaccine against cancer possible?
Vaccination with embryonic stem cells protects against lung cancer: is a broad-spectrum prophylactic vaccine against cancer possible?
复制标题
DOI：
10.1371/journal.pone.0042289
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Eaton JW
中科院分区：
文献类型：
--
作者：
Yaddanapudi K;Mitchell RA;Putty K;Willer S;Sharma RK;Yan J;Bodduluri H;Eaton JW
肿瘤和胚胎之间的抗原相似性多年来一直受到人们的重视，这反映了癌细胞和/或癌症起始干细胞表达胚胎基因产物。利用这种相似性，我们测试了一种由同种异体鼠胚胎干细胞（ESC）组成的预防性肺癌疫苗。首次使用的 C57BL/6 小鼠接种了 ESC 以及粒细胞巨噬细胞集落刺激因子 (GM-CSF)，以提供免疫刺激佐剂活性。接种疫苗的小鼠可以免受随后植入式刘易斯肺癌（LLC）的攻击。 ESC诱导的抗肿瘤免疫并不是由于非特异性“同种异体反应”，因为用同种异体小鼠胚胎成纤维细胞进行疫苗接种并不能防止肿瘤生长。疫苗功效与强大的肿瘤反应性原发性和记忆性 CD8+ T 效应器反应、Th1 细胞因子反应、较高的瘤内 CD8+ T 效应器/CD4+CD25+Foxp3+ T 调节细胞比率以及脾脏中骨髓源性抑制细胞的减少有关。研究发现，预防肿瘤发生需要 CD8 介导的细胞毒性 T 淋巴细胞 (CTL) 反应，因为体内 CD8+ T 淋巴细胞的消耗完全消除了疫苗接种的保护作用。重要的是，这种疫苗接种策略还抑制了由致癌物质给药和慢性肺部炎症联合诱导的肺癌的发展。进一步完善这种新型疫苗策略和鉴定共享的 ESC/肿瘤抗原可能会为肺癌患者带来免疫治疗选择，也许更重要的是，可能代表着预防性癌症疫苗开发的第一步。
The antigenic similarity between tumors and embryos has been appreciated for many years and reflects the expression of embryonic gene products by cancer cells and/or cancer-initiating stem cells. Taking advantage of this similarity, we have tested a prophylactic lung cancer vaccine composed of allogeneic murine embryonic stem cells (ESC). Naïve C57BL/6 mice were vaccinated with ESC along with a source of granulocyte macrophage-colony stimulating factor (GM-CSF) in order to provide immunostimulatory adjuvant activity. Vaccinated mice were protected against subsequent challenge with implantable Lewis lung carcinoma (LLC). ESC-induced anti-tumor immunity was not due to a non-specific “allo-response” as vaccination with allogeneic murine embryonic fibroblasts did not protect against tumor outgrowth. Vaccine efficacy was associated with robust tumor-reactive primary and memory CD8+ T effector responses, Th1 cytokine response, higher intratumoral CD8+ T effector/CD4+CD25+Foxp3+ T regulatory cell ratio, and reduced myeloid derived suppressor cells in the spleen. Prevention of tumorigenesis was found to require a CD8-mediated cytotoxic T lymphocyte (CTL) response because in vivo depletion of CD8+ T lymphocytes completely abrogated the protective effect of vaccination. Importantly, this vaccination strategy also suppressed the development of lung cancer induced by the combination of carcinogen administration and chronic pulmonary inflammation. Further refinement of this novel vaccine strategy and identification of shared ESC/tumor antigens may lead to immunotherapeutic options for lung cancer patients and, perhaps more importantly, could represent a first step toward the development of prophylactic cancer vaccines.
登录
查看更多内容
影响因子：
5.2
作者：
Li, Yi;Zeng, Hui;Li, Zihai
通讯作者：
Li, Zihai
影响因子：
11.2
作者：
Gu, Guangyu;Yuan, Jialing;Kasper, Susan
通讯作者：
Kasper, Susan
影响因子：
4.7
作者：
Kisley, LR;Barrett, BS;Malkinson, AM
通讯作者：
Malkinson, AM
DOI：
10.1038/newbio234153a0
发表时间：
1971-01-01
期刊：
NATURE-NEW BIOLOGY
影响因子：
--
作者：
KLAVINS, JV;MESATEJA.R;WEISS, M
通讯作者：
WEISS, M
DOI：
10.1084/jem.122.3.467
发表时间：
1965-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gold P;Freedman SO
通讯作者：
Freedman SO