Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasília, Brazil.
Department of Cellular Biology, Institute of Biological Sciences, University of Brasilia, Brasília, Brazil.
Curr Pharm Des. 2024;30(31):2493-2504. doi: 10.2174/0113816128316870240610045550.
Cancer is an individual disease and its formation and development are specific to each host. Conventional treatments are ineffective in complex cases, such as metastasis, and have severe adverse side effects. New strategies are needed to address the problem, and the use of immunogenic cell death (ICD) as a trigger or booster of the immune system through the exposure of damage-associated molecular patterns, along with tumor antigens, by cancerous cells is presented as an immunization approach in this work.
For this purpose, 4T1 cells were exposed to doxorubicin (DOX) for 24 hours and then, these cells undergoing ICD were subcutaneously administered to mice. The ICD induction by DOX on 4T1 was assessed by flow cytometry and image analysis. This immunization process was performed three times and after the last administration, the immunized mice were challenged with a subcutaneous xenograft of live cancer cells.
The results demonstrate that the mice immunized with cells undergoing ICD after exposure to DOX presented no primary tumor or indications of distant metastatic lesion development.
In summary, our findings indicate that the immunization process utilizing ICD is indeed efficacious in managing this aggressive form of pre-clinical breast cancer.
癌症是一种个体疾病，其形成和发展对每个宿主都是特异的。传统治疗方法在复杂情况下（如转移）无效，且具有严重的不良反应。需要新的策略来解决这个问题，本研究提出了一种通过使癌细胞暴露损伤相关分子模式和肿瘤抗原来引发或增强免疫系统的免疫原性细胞死亡（ICD）作为一种免疫接种方法。
为此，将 4T1 细胞用多柔比星（DOX）孵育 24 小时，然后将经历 ICD 的这些细胞皮下注射到小鼠中。通过流式细胞术和图像分析评估 DOX 对 4T1 的 ICD 诱导作用。进行了三次免疫接种过程，最后一次给药后，用活癌细胞的皮下异种移植物对免疫小鼠进行攻击。
结果表明，用 DOX 处理后经历 ICD 的细胞免疫的小鼠没有原发性肿瘤或远处转移病灶发展的迹象。
总之，我们的研究结果表明，利用 ICD 的免疫接种过程在治疗这种侵袭性临床前乳腺癌方面确实有效。
