CD4+ T cells play a critical role in the generation of primary and memory antitumor immune responses elicited by SA-4-1BBL and TAA-based vaccines in mouse tumor models.
CD4+ T cells play a critical role in the generation of primary and memory antitumor immune responses elicited by SA-4-1BBL and TAA-based vaccines in mouse tumor models.
复制标题
DOI：
10.1371/journal.pone.0073145
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Shirwan H
中科院分区：
文献类型：
--
作者：
Sharma RK;Yolcu ES;Srivastava AK;Shirwan H
CD 4 + T细胞在癌症不同免疫治疗环境中产生治疗性原发性和记忆性免疫应答中的作用仍然不明确。我们在此研究了这一问题，使用两种疫苗制剂含有一种新的共刺激分子，SA-4-1BBL，作为佐剂和HPV E7或生存素（SVN）作为肿瘤相关抗原（TAA）在两个小鼠移植性肿瘤模型; TC-1宫颈癌表达异种HPV E7和3LL肺癌过表达自体SVN。用优化的SA-4-1BBL/TAA制剂单次接种导致两种模型中>70%的小鼠中6天建立的TC-1和3LL肿瘤的根除。在肿瘤攻击前一天体内耗尽CD 4 + T细胞导致TC-1（25%）和3LL（12.5%）肿瘤模型中疫苗效力受损。与此形成鲜明对比的是，肿瘤攻击后5天和疫苗接种前1天的CD 4 + T细胞耗竭并没有显著改变这些疫苗的治疗功效。然而，长期免疫记忆在3LL中受到损害，但在TC-1模型中没有，因为当在初始肿瘤接种后60天用3LL细胞再攻击时，显著数量（85.7%）的无肿瘤小鼠死于肿瘤生长。总的来说，这些结果证明了CD 4 + T细胞在由基于SA-4-1BBL/TAA的疫苗引起的治疗性初次免疫应答的产生中发挥的不可或缺的作用，而不管TAA的性质如何，并且确立了CD 4 + T细胞对于针对表达自身抗原SVN的3LL肿瘤而不是表达异种病毒抗原E7的TC-1的长期免疫记忆的重要性。
The role of CD4+ T cells in the generation of therapeutic primary and memory immune responses in cancer diverse immunotherapy settings remains ambiguous. We herein investigated this issue using two vaccine formulations containing a novel costimulatory molecule, SA-4-1BBL, as adjuvant and HPV E7 or survivin (SVN) as tumor associated antigens (TAAs) in two mouse transplantable tumor models; the TC-1 cervical cancer expressing xenogeneic HPV E7 and 3LL lung carcinoma overexpressing autologous SVN. Single vaccination with optimized SA-4-1BBL/TAA formulations resulted in the eradication of 6-day established TC-1 and 3LL tumors in >70% of mice in both models. The in vivo depletion of CD4+ T cells one day before tumor challenge resulted in compromised vaccine efficacy in both TC-1 (25%) and 3LL (12.5%) tumor models. In marked contrast, depletion of CD4+ T cells 5 days post-tumor challenge and one day prior to vaccination did not significantly alter the therapeutic efficacy of these vaccines. However, long-term immunological memory was compromised in the 3LL, but not in TC-1 model as a significant number (85.7%) of tumor free-mice succumbed to tumor growth when rechallenged with 3LL cells 60 days after the initial tumor inoculation. Collectively, these results demonstrate the indispensable role CD4+ T cells play in the generation of therapeutic primary immune responses elicited by SA-4-1BBL/TAA-based vaccines irrespective of the nature of TAAs and establish the importance of CD4+ T cells for long-term immune memory against 3LL tumor expressing self-antigen SVN, but not TC-1 expressing xenogeneic viral antigen E7.
登录
查看更多内容
DOI：
10.1084/jem.176.2.553
发表时间：
1992-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guerder S;Matzinger P
通讯作者：
Matzinger P
影响因子：
5.5
作者：
Sharma, Rajesh K.;Srivastava, Abhishek K.;Yolcu, Esma S.;MacLeod, Kathryn J.;Schabowsky, Rich-Henry;Madireddi, Shravan;Shirwan, Haval
通讯作者：
Shirwan, Haval
影响因子：
4.4
作者：
Dolfi, Douglas V.;Duttagupta, Priyanka A.;Katsikis, Peter D.
通讯作者：
Katsikis, Peter D.
影响因子：
4.4
作者：
Bullock, TNJ;Yagita, H
通讯作者：
Yagita, H
影响因子：
5.4
作者：
FELTKAMP, MCW;SMITS, HL;KAST, WM
通讯作者：
KAST, WM