Sabel Michael S, Nehs Matthew A, Su Gang, Lowler Kathleen P, Ferrara James L M, Chang Alfred E
University of Michigan, 3304 Cancer Center, East Medical Center, 1500 East Medical Center, Ann Arbor, MI 48109-0932, USA.
Breast Cancer Res Treat. 2005 Mar;90(1):97-104. doi: 10.1007/s10549-004-3289-1.
With improvements in breast imaging and image-guided interventions, there is interest in ablative techniques for breast cancer. Cryosurgery initiates inflammation and leaves tumor-specific antigens intact, which may induce an anti-tumor immune response. To help define the mechanisms involved in the cryoimmunologic response, we compared cryosurgery to surgery in a murine model of breast cancer.
BALB/c mice with MT-901 tumors underwent cryoablation or resection. Mice successfully treated were re-challenged with MT-901 or RENCA. Serum cytokine levels were analyzed by ELISA. Tumor draining lymph nodes (TDLN) and spleens were harvested, lymphocytes were activated and assessed for a specific anti-tumor response by both an interferon-gamma (IFNgamma) release assay and ELISPOT. NK cell activity was assessed by cytotoxicity against YAC-1, an NK-susceptible cell line.
After re-challenge, tumors developed in 86% of mice treated by surgical excision compared to 16% of mice treated by cryosurgery (p=0.025). Cryoablation of MT-901 had no effect on re-challenge with RENCA. Cryoablation led to significantly higher levels of interleukin (IL)-12 (383.6 pg/ml +/- 32.8 versus 251.6 +/- 16.5, p=0.025) and IFN-gamma (1564 pg/ml +/- 49 versus 1244 pg/ml +/- 101, p=0.009), but no changes in IL-4 or IL-10. Tumor-specific T-cell responses were evident after cryosurgery in lymphocytes from TDLN but not from spleen. Cryoablation also increased NK activity compared to surgery (24.5% +/- 17.3 versus 16.5% +/- 5.9, p < 0.001).
Cryoablation results in the induction of both a tumor-specific T-cell response in the TDLN and increased systemic NK cell activity, which correlates with rejection of tumors upon re-challenge.
随着乳腺成像和图像引导介入技术的改进，人们对乳腺癌的消融技术产生了兴趣。冷冻手术引发炎症并使肿瘤特异性抗原保持完整，这可能诱导抗肿瘤免疫反应。为了帮助确定冷冻免疫反应所涉及的机制，我们在乳腺癌小鼠模型中将冷冻手术与手术进行了比较。
患有MT - 901肿瘤的BALB/c小鼠接受冷冻消融或切除手术。成功治疗的小鼠再次用MT - 901或RENCA进行攻击。通过酶联免疫吸附测定（ELISA）分析血清细胞因子水平。收集肿瘤引流淋巴结（TDLN）和脾脏，激活淋巴细胞，并通过干扰素-γ（IFNγ）释放测定和酶联免疫斑点法（ELISPOT）评估特异性抗肿瘤反应。通过对YAC - 1（一种NK敏感细胞系）的细胞毒性评估NK细胞活性。
再次攻击后，手术切除治疗的小鼠中有86%出现肿瘤，而冷冻手术治疗的小鼠中这一比例为16%（p = 0.025）。MT - 901的冷冻消融对RENCA再次攻击没有影响。冷冻消融导致白细胞介素（IL）- 12水平显著升高（383.6 pg/ml ± 32.8对251.6 ± 16.5，p = 0.025）和IFN - γ水平显著升高（1564 pg/ml ± 49对1244 pg/ml ± 101，p = 0.009），但IL - 4或IL - 10没有变化。冷冻手术后，TDLN中的淋巴细胞出现肿瘤特异性T细胞反应，但脾脏中的淋巴细胞未出现。与手术相比，冷冻消融还增加了NK活性（24.5% ± 17.3对16.5% ± 5.9，p < 0.001）。
冷冻消融导致TDLN中诱导肿瘤特异性T细胞反应，并增加全身NK细胞活性，这与再次攻击时肿瘤的排斥相关。
