利用甲氨蝶呤产生的免疫原性细胞裂解物控制侵袭性4T1-luc转移性乳腺癌

IF 6.9 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Luana Cristina Camargo , Pedro Burgel , Camila Magalhães Cardador , Victor Carlos Mello , Karen Letycia Rodrigues de Paiva , Marina Mesquita Simões , Raffael Júnio Araújo de Castro , Isabel Martinello Valente , Gabriel Ribeiro Farias , Thais Bergmann de Castro , Luís Alexandre Muehlmann , Sônia Nair Báo , João Paulo Figueiró Longo
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引用次数: 0

摘要

本研究研究了一种新的免疫治疗临床前侵袭性转移性乳腺癌的方法,使用顺铂和甲氨蝶呤治疗4T1-luc细胞的免疫原性细胞溶解物,解决了与乳腺癌转移相关的不良预后和显著死亡率的改善治疗的迫切需要。甲氨蝶呤是一种传统的细胞毒性药物,显示出一种以前未被认识到的诱导免疫原性细胞裂解的能力,这为药物重新定位提供了潜在的机会。在小鼠IV期转移性乳腺癌模型中,通过生物发光成像评估,用这些裂解物免疫可显著降低原发肿瘤生长和肺转移。通过细胞因子分析(IL-6和IFN-γ)和CD4 + 和CD8 + T细胞亚群的流式细胞术分析可以证明,免疫还可以调节免疫细胞群,减少脾和肝肿大,并部分逆转与4T1-luc肿瘤生长相关的免疫抑制表型。具体来说,甲氨蝶呤处理的裂解物诱导CD4 + T细胞向效应表型的显著转变。这些发现强调了这种免疫治疗方法改善乳腺癌治疗结果的潜力,值得进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Control of aggressive 4T1-luc metastatic breast cancer using immunogenic cell lysates generated with methotrexate
This study investigated a novel immunization therapy for pre-clinical aggressive metastatic breast cancer using immunogenic cell lysates derived from 4T1-luc cells treated with cisplatin and methotrexate, addressing the critical need for improved treatments given the poor prognosis associated with breast cancer metastasis and its significant mortality rate. Methotrexate, a conventional cytotoxic agent, demonstrated a previously unrecognized capacity to induce immunogenic cell lysates, presenting a potential drug repositioning opportunity. In a murine model of stage IV metastatic breast cancer, immunization with these lysates significantly reduced primary tumor growth and lung metastasis, as assessed by bioluminescence imaging. Immunization also modulated immune cell populations, reducing splenomegaly and hepatomegaly, and partially reversing the immunosuppressive phenotype associated with 4T1-luc tumor growth, as evidenced by cytokine profiling (IL-6 and IFN-γ) and flow cytometry analysis of CD4 + and CD8 + T cell subpopulations. Specifically, methotrexate-treated lysates induced a significant shift in CD4 + T cells towards an effector phenotype. These findings highlight the potential of this immunotherapy approach to improve breast cancer treatment outcomes and warrant further investigation.
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来源期刊
CiteScore
11.90
自引率
2.70%
发文量
1621
审稿时长
48 days
期刊介绍: Biomedicine & Pharmacotherapy stands as a multidisciplinary journal, presenting a spectrum of original research reports, reviews, and communications in the realms of clinical and basic medicine, as well as pharmacology. The journal spans various fields, including Cancer, Nutriceutics, Neurodegenerative, Cardiac, and Infectious Diseases.
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