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采用经原发性肿瘤冷冻消融致敏的淋巴结细胞对乳腺癌进行过继性免疫治疗。

Adoptive immunotherapy of breast cancer with lymph node cells primed by cryoablation of the primary tumor.

作者信息

Sabel Michael S, Arora Alisha, Su Gang, Chang Alfred E

机构信息

University of Michigan, Department of Surgery, Division of Surgical Oncology, 3304 Cancer Center, 1500 East Medical Center, Ann Arbor, MI 48109-0932, USA.

出版信息

Cryobiology. 2006 Dec;53(3):360-6. doi: 10.1016/j.cryobiol.2006.07.004. Epub 2006 Sep 14.

Abstract

Cryoablation of cancer leaves tumor-associated antigens intact in an inflammatory microenvironment that can stimulate a regional anti-tumor immune response. We examined whether cryoablated tumor draining lymph nodes (CTDLN) as adoptive immunotherapy may be an effective immunotherapeutic approach in the adjuvant treatment of breast cancer. BALB/c mice with MT-901 mammary adenocarcinoma tumors underwent cryoablation, resection or no treatment and tumor draining lymph nodes were harvested. Cryoablation resulted in only a mild increase in the absolute number of T-cells but a significant increase in the fraction of tumor-specific T-cells as evidenced on IFN-gamma release assay. FACS analysis demonstrated no significant relative shift in the proportion of CD4(+) or CD8(+) cells. The adoptive transfer of CTDLN resulted in a significant reduction of pulmonary metastases as compared to TDLN from either tumor-bearing mice or mice who underwent surgical excision. Cryoablation prior to surgical resection of breast cancer can be used as a method to generate effector T-cells for adjuvant adoptive cellular immunotherapy.

摘要

癌症冷冻消融可使肿瘤相关抗原在炎症微环境中保持完整,该微环境可刺激局部抗肿瘤免疫反应。我们研究了作为过继性免疫疗法的冷冻消融肿瘤引流淋巴结(CTDLN)是否可能是乳腺癌辅助治疗中的一种有效免疫治疗方法。对患有MT - 901乳腺腺癌肿瘤的BALB / c小鼠进行冷冻消融、切除或不治疗,并收集肿瘤引流淋巴结。冷冻消融仅导致T细胞绝对数量轻度增加,但肿瘤特异性T细胞比例显著增加,这在干扰素-γ释放试验中得到证实。流式细胞术分析显示CD4(+)或CD8(+)细胞比例无明显相对变化。与来自荷瘤小鼠或接受手术切除小鼠的TDLN相比,CTDLN的过继性转移导致肺转移显著减少。乳腺癌手术切除前进行冷冻消融可作为一种为辅助性过继性细胞免疫治疗产生效应T细胞的方法。

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