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供体淋巴细胞输注治疗后CT26结肠肿瘤小鼠T淋巴细胞亚群的变化

Changes in T lymphocyte subsets in mice with CT26 colon tumors after treatment with donor lymphocyte infusion.

作者信息

Jiang Tao, Piao Daxun, Zhu Anlong, Jiang Hongchi

机构信息

Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Str, Nangang District, Harbin, Heilongjiang Province, People's Republic of China.

出版信息

Tumour Biol. 2014 Jun;35(6):5599-605. doi: 10.1007/s13277-014-1740-4. Epub 2014 Mar 22.

DOI:10.1007/s13277-014-1740-4
PMID:24659423
Abstract

The objective of this study was to detect changes in T lymphocyte subpopulations in mice with CT26 subcutaneous colon cancer after treatment with donor lymphocyte infusion (DLI) and cyclophosphamide (CP) chemotherapy. A colon cancer model was established by subcutaneous injection of CT26 carcinoma cells into BALB/C mice. The mice were randomized into different treatment groups. We recorded survival times, tumor growth inhibition rates, histopathological changes, and T lymphocyte subsets in peripheral blood of the mice. Mice treated with DLI and CP survived 33.5 ± 5.02 days, which was significantly longer than the survival time of untreated control mice (16.7 ± 2.98 days, P < 0.01). In addition, the tumor inhibitory rate was higher in mice treated with DLI and CP (89.3 %) than that in mice treated with CP or DLI alone (67.1 and 34.5 %, respectively). There were higher levels of T lymphocytes that were CD3(+) and CD4(+) in mice treated with DLI alone or the combination of CP and DLI (P < 0.05), and the ratio of CD4(+)/CD8(+) cells was significantly improved in these mice (P < 0.05). DLI combined with chemotherapy significantly prolonged survival and inhibited tumor growth in mice with CT26 colon cancer. This treatment might also improve immune function in these mice. Donor spleen cells that include high numbers of allogeneic lymphocytes and a few stem cells could induce a graft-versus-tumor effect, leading to elimination of residual cancer cells. This indicates that it is potentially a feasible adoptive cellular immunotherapy strategy for the management of solid tumors.

摘要

本研究的目的是检测供体淋巴细胞输注(DLI)和环磷酰胺(CP)化疗后CT26皮下结肠癌小鼠T淋巴细胞亚群的变化。通过将CT26癌细胞皮下注射到BALB/C小鼠中建立结肠癌模型。将小鼠随机分为不同的治疗组。我们记录了小鼠的生存时间、肿瘤生长抑制率、组织病理学变化以及外周血中的T淋巴细胞亚群。接受DLI和CP治疗的小鼠存活了33.5±5.02天,显著长于未治疗的对照小鼠的生存时间(16.7±2.98天,P<0.01)。此外,接受DLI和CP治疗的小鼠的肿瘤抑制率(89.3%)高于单独接受CP或DLI治疗的小鼠(分别为67.1%和34.5%)。单独接受DLI或CP与DLI联合治疗的小鼠中,CD3(+)和CD4(+)的T淋巴细胞水平较高(P<0.05),并且这些小鼠中CD4(+)/CD8(+)细胞的比例显著提高(P<0.05)。DLI联合化疗显著延长了CT26结肠癌小鼠的生存期并抑制了肿瘤生长。这种治疗方法还可能改善这些小鼠的免疫功能。包含大量同种异体淋巴细胞和少量干细胞的供体脾细胞可诱导移植物抗肿瘤效应,导致残留癌细胞的清除。这表明它可能是一种用于实体瘤治疗的可行的过继性细胞免疫治疗策略。

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本文引用的文献

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XRCC1 and GSTP1 polymorphisms and prognosis of oxaliplatin-based chemotherapy in colorectal cancer: a meta-analysis.XRCC1 和 GSTP1 多态性与结直肠癌奥沙利铂为基础的化疗预后的关系:一项荟萃分析。
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Immune reconstitution and graft-versus-host reactions in rat models of allogeneic hematopoietic cell transplantation.同种异体造血细胞移植大鼠模型中的免疫重建和移植物抗宿主反应。
Front Immunol. 2012 Nov 30;3:355. doi: 10.3389/fimmu.2012.00355. eCollection 2012.
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A meta-analysis of the effects of chemotherapy on cognition in patients with cancer.一项关于化疗对癌症患者认知功能影响的荟萃分析。
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