<br>阿霉素诱导的免疫原性细胞死亡损害 4T1 乳腺癌肿瘤模型中的肿瘤进展和远处转移,Current Pharmaceutical Design

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阿霉素诱导的免疫原性细胞死亡损害 4T1 乳腺癌肿瘤模型中的肿瘤进展和远处转移
Current Pharmaceutical Design ( IF 2.6 ) Pub Date : 2024-07-22 , DOI: 10.2174/0113816128316870240610045550
Camila Magalhães Cardador ₁ , Thaís Bergmann de Castro ₂ , Raffael Júnio Araújo de Castro ₂ , Anamélia Lorenzetti Bocca ₂ , Luana Cristina Camargo ₁ , Thyago Arruda Pacheco ₁ , Luís Alexandre Muehlmann ₃ , João Paulo Figueiró Longo ₁

Affiliation

简介：癌症是一种单独的疾病，其形成和发展因每个宿主而异。常规治疗对转移等复杂病例无效，并且有严重的不良副作用。需要新的策略来解决这个问题，在这项工作中，通过暴露癌细胞的损伤相关分子模式和肿瘤抗原，使用免疫原性细胞死亡（ICD）作为免疫系统的触发或助推器作为免疫系统的触发或助推器。方法：为此，将 4T1 细胞暴露于阿霉素（DOX） 24 小时，然后将这些接受 ICD 的细胞皮下注射给小鼠。通过流式细胞术和图像分析评估 DOX 对 4T1 的 ICD 诱导。该免疫过程进行了 3 次，在最后一次给药后，用活癌细胞的皮下异种移植物攻击免疫的小鼠。结果：结果表明，暴露于 DOX 后用接受 ICD 的细胞免疫的小鼠没有表现出原发性肿瘤或远处转移病灶发展的迹象。结论：总之，我们的研究结果表明，利用 ICD 的免疫过程确实可以有效地控制这种侵袭性的临床前乳腺癌。

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Doxorubicin-induced Immunogenic Cell Death Impairs Tumor Progression and Distant Metastasis in a 4T1 Breast Cancer Tumor Model

Introduction: 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. Methods: 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. Results: 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. Conclusion: In summary, our findings indicate that the immunization process utilizing ICD is indeed efficacious in managing this aggressive form of pre-clinical breast cancer.

更新日期：2024-07-22

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