Increased antitumor effects using IL-2 with anti-TGF-β reveals competition between mouse NK and CD8 T cells.
Increased antitumor effects using IL-2 with anti-TGF-β reveals competition between mouse NK and CD8 T cells.
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DOI：
10.4049/jimmunol.1400034
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发表时间：
2014-08-15
期刊：
影响因子：
--
通讯作者：
Murphy WJ
中科院分区：
文献类型：
--
作者：
Alvarez M;Bouchlaka MN;Sckisel GD;Sungur CM;Chen M;Murphy WJ
由于对去除癌症中的免疫抑制途径的兴趣日益增加，评估了IL 2与抗体的组合以中和TGFβ（一种有效的免疫抑制细胞因子）。联合免疫疗法导致显著更大的抗肿瘤作用。这些与NK细胞、NK祖细胞和活化的CD8 T细胞的数量和功能的显著增加相关，导致观察到的抗肿瘤作用。联合免疫治疗也伴随着比单独IL 2治疗更少的毒性。此外，我们观察到NK和活化的CD8 T细胞之间的双重竞争，使得在免疫治疗后，任一效应物群体的消耗导致另一群体的总扩增增加和补偿性抗肿瘤作用。这项研究证明了这种联合免疫治疗方案作为一种有前途的癌症治疗方法的功效，并说明了NK和CD 8 T细胞之间存在有效的竞争性调节途径来响应全身激活。
Due to increasing interest in the removal of immunosuppressive pathways in cancer, the combination of IL2 with antibodies to neutralize TGFβ, a potent immunosuppressive cytokine, was assessed. Combination immunotherapy resulted in significantly greater anti-tumor effects. These were correlated with significant increases in the numbers and functionality of NK cells, NK progenitors and activated CD8 T cells resulting in the observed anti-tumor effects. Combination immunotherapy was also accompanied with lesser toxicities than IL2 therapy alone. Additionally, we observed a dual competition between NK and activated CD8 T cells such that after immunotherapy, the depletion of either effector population resulted in the increased total expansion of the other population and compensatory anti-tumor effects. This study demonstrates the efficacy of this combination immunotherapeutic regimen as a promising cancer therapy and illustrates the existence of potent competitive regulatory pathways between NK and CD8 T cells in response to systemic activation.
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影响因子：
41.2
作者：
通讯作者：
--
DOI：
10.1084/jem.20131219
发表时间：
2013-10-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bouchlaka MN;Sckisel GD;Chen M;Mirsoian A;Zamora AE;Maverakis E;Wilkins DE;Alderson KL;Hsiao HH;Weiss JM;Monjazeb AM;Hesdorffer C;Ferrucci L;Longo DL;Blazar BR;Wiltrout RH;Redelman D;Taub DD;Murphy WJ
通讯作者：
Murphy WJ
影响因子：
4.4
作者：
Barber, Melissa A.;Zhang, Tong;Sentman, Charles L.
通讯作者：
Sentman, Charles L.
影响因子：
30.5
作者：
Andrews, DM;Scalzo, AA;Degli-Esposti, MA
通讯作者：
Degli-Esposti, MA
影响因子：
20.3
作者：
Buyse, Marc;Squifflet, Pierre;Burzykowski, Tomasz
通讯作者：
Burzykowski, Tomasz