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
{"title":"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","authors":"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","doi":"10.1016/j.biopha.2025.118079","DOIUrl":null,"url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118079"},"PeriodicalIF":6.9000,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Control of aggressive 4T1-luc metastatic breast cancer using immunogenic cell lysates generated with methotrexate\",\"authors\":\"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\",\"doi\":\"10.1016/j.biopha.2025.118079\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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.</div></div>\",\"PeriodicalId\":8966,\"journal\":{\"name\":\"Biomedicine & Pharmacotherapy\",\"volume\":\"187 \",\"pages\":\"Article 118079\"},\"PeriodicalIF\":6.9000,\"publicationDate\":\"2025-04-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomedicine & Pharmacotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0753332225002732\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedicine & Pharmacotherapy","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0753332225002732","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
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.
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.