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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >Activated NKT cells and NK cells render T cells resistant to myeloid-derived suppressor cells and result in an effective adoptive cellular therapy against breast cancer in the FVBN202 transgenic mouse.
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Activated NKT cells and NK cells render T cells resistant to myeloid-derived suppressor cells and result in an effective adoptive cellular therapy against breast cancer in the FVBN202 transgenic mouse.

机译：活化的NKT细胞和NK细胞使T细胞对源自髓样的抑制细胞产生抗性，并导致FVBN202转基因小鼠对乳腺癌有效的过继性细胞疗法。

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摘要

Attempts to cure breast cancer by adoptive cellular therapy (ACT) have not been successful. This is primarily due to the presence of tumor-induced immune-suppressive mechanisms as well as the failure of tumor-reactive T cells to provide long-term memory responses in vivo. To address these clinically important challenges, we developed an ex vivo protocol for the expansion of tumor-reactive immune cells obtained from tumor-bearing animals prior to or after local radiation therapy. We used an Ag-free protocol that included bryostatin 1/ionomycin and sequential common gamma-chain cytokines (IL-7/IL-15 + IL-2). The proposed protocol expanded tumor-reactive T cells as well as activated non-T cells, including NKT cells, NK cells, and IFN-gamma-producing killer dendritic cells. Antitumor efficacy of T cells depended on the presence of non-T cells. The effector non-T cells also rendered T cells resistant to myeloid-derived suppressor cells. Radiation therapy altered phenotypic distribution and differentiation of T cells as well as their ability to generate central memory T cells. ACT by means of the expanded cells protected animals from tumor challenge and generated long-term memory responses against the tumor, provided that leukocytes were derived from tumor-bearing animals prior to radiation therapy. The ex vivo protocol was also able to expand HER-2eu-specific T cells derived from the PBMC of a single patient with breast carcinoma. These data suggest that the proposed ACT protocol should be studied further in breast cancer patients.
机译：通过过继细胞疗法（ACT）治愈乳腺癌的尝试尚未成功。这主要是由于存在肿瘤诱导的免疫抑制机制，以及肿瘤反应性T细胞无法在体内提供长期记忆反应。为了解决这些临床上重要的挑战，我们开发了一种体外实验方案，用于扩增在局部放疗之前或之后从荷瘤动物身上获得的肿瘤反应性免疫细胞。我们使用了不含Ag的方案，其中包括抑菌素1 /离子霉素和顺序常见的γ链细胞因子（IL-7 / IL-15 + IL-2）。拟议的协议扩大了肿瘤反应性T细胞以及激活的非T细胞，包括NKT细胞，NK细胞和产生IFN-γ的杀伤树突状细胞。 T细胞的抗肿瘤功效取决于非T细胞的存在。效应子非T细胞也使T细胞对源自髓样的抑制细胞具有抗性。放射疗法改变了T细胞的表型分布和分化，以及它们产生中枢记忆T细胞的能力。前提是白细胞是放射治疗前来自荷瘤动物的白细胞，通过扩张细胞的ACT可以保护动物免受肿瘤攻击并产生针对肿瘤的长期记忆反应。离体方案还能够扩增源自单个乳腺癌患者PBMC的HER-2 / neu特异性T细胞。这些数据表明，拟议的ACT方案应在乳腺癌患者中进一步研究。

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