Adoptive transfer of HER2/neu-specific T cells expanded with alternating gamma chain cytokines mediate tumor regression when combined with the depletion of myeloid-derived suppressor cells.
Adoptive transfer of HER2/neu-specific T cells expanded with alternating gamma chain cytokines mediate tumor regression when combined with the depletion of myeloid-derived suppressor cells.
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DOI：
10.1007/s00262-008-0609-z
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发表时间：
2009-06
影响因子：
5.8
通讯作者：
Manjili, Masoud H.
中科院分区：
文献类型：
--
作者：
Morales, Johanna K.;Kmieciak, Maciej;Graham, Laura;Feldmesser, Marta;Bear, Harry D.;Manjili, Masoud H.
关键词：
过继免疫疗法（AIT）使用体外扩增的HER-2/新特异性T细胞对骨髓中弥散性肿瘤细胞显示出初步的有希望的结果。然而，它未能促进对原发性肿瘤的客观反应。我们首次报道了体外交替γ链细胞因子（IL-2， IL-7和IL-15）可以扩增新特异性淋巴细胞，从而在体外杀死乳腺肿瘤。然而，在FVBN202转基因乳腺癌小鼠模型的癌前阶段，这些新特异性T细胞的抗肿瘤功效受到骨髓源性抑制细胞（MDSC）水平升高的影响。在体内，AIT联合MDSC的消耗导致新阳性原发肿瘤的消退。重要的是，只有当AIT与MDSC结合使用时，新特异性抗体反应才会恢复。体外研究确定MDSC以接触依赖的方式抑制T细胞增殖。总之，这些结果表明，AIT与MDSC的消耗或抑制联合使用可能导致乳腺肿瘤的消退。
Adoptive immunotherapy (AIT) using ex vivo-expanded HER-2/neu-specific T cells has shown initial promising results against disseminated tumor cells in the bone marrow. However, it has failed to promote objective responses against primary tumors. We report for the first time that alternating gamma chain cytokines (IL-2, IL-7 and IL-15) ex vivo can expand the neu-specific lymphocytes that can kill breast tumors in vitro. However, the anti-tumor efficacy of these neu-specific T cells was compromised by the increased levels of myeloid-derived suppressor cells (MDSC) during the premalignant stage in FVBN202 transgenic mouse model of breast carcinoma. Combination of AIT with the depletion of MDSC, in vivo, resulted in the regression of neu positive primary tumors. Importantly, neu-specific antibody responses were restored only when AIT was combined with the depletion of MDSC. In vitro studies determined that MDSC caused inhibition of T cell proliferation in a contact-dependent manner. Together, these results suggest that combination of AIT with depletion or inhibition of MDSC could lead to the regression of mammary tumors.
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影响因子：
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通讯作者：
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