pH-responsive polymer micelles reshape the immune microenvironment of PIK3CA-mutated Luminal breast cancer
10.12354/j.issn.1000-8179.2025.20250105
- VernacularTitle:pH响应聚合物胶束重塑PIK3CA突变Luminal型乳腺癌免疫微环境
- Author:
Yang CHENJU
1
;
Wang SILEI
;
Chen GUIDONG
;
Wang FANCHEN
;
Li XINGCHEN
;
Xu LINLIN
;
Shi LINQI
;
Yu JINPU
Author Information
1. 天津医科大学肿瘤医院肿瘤分子诊断中心,国家恶性肿瘤临床医学研究中心,天津市恶性肿瘤临床医学研究中心,乳腺癌防治教育部重点实验室,天津市肿瘤免疫与生物治疗重点实验室(天津市 300060)
- Publication Type:Journal Article
- Keywords:
Luminal breast cancer;
PIK3CA;
myeloid-derived suppressor cells(MDSCs);
polymer micelles
- From:
Chinese Journal of Clinical Oncology
2025;52(6):271-278
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of PIK3CA mutations on the tumor immune microenvironment in Luminal breast cancer and evaluate the potential of Alpelisib-loaded pH-responsive polymer micelles in modulating the tumor immune microenvironment.Methods:PIK3CA mutations in breast cancer were analyzed using bioinformatics tools.A mouse xenograft model of Luminal breast cancer harboring a PIK3CA mutation was established,and alterations in the tumor immune microenvironment were examined using mass cytometry(CyTOF).During the period from August 2004 to December 2008 in Tianjin Medical University Cancer Hospital,tissue biopsies of 62 Luminal breast cancer patients in the BRCA cohort were collected Study the relationship between PIK3CA mutations and tumor immune microenvironment at the organizational level.Alpelisib-loaded polymer micelles(Alpelisib@MSPM)were synthesized,characterized,and evaluated for thera-peutic efficacy in Luminal breast cancer with PIK3CA mutations.Results:PIK3CA is one of the most frequently mutated genes in breast can-cer,with the highest prevalence in Luminal subtypes.CyTOF analysis demonstrated that PIK3CA mutations contribute to a tumor immun-osuppressive microenvironment in xenografts.Multiplex fluorescence immunohistochemistry revealed that PIK3CA-mutated tumors exhib-ited more infiltration of myeloid-derived suppressor cells(MDSCs)and less infiltration of CD8? T cells.The synthesized Alpelisib-loaded pH-re-sponsive polymer micelles had an average size of approximately 127 nm.Treatment with Alpelisib and Alpelisib@MSPM reduced tumor growth in mice with PIK3CA-mutated Luminal breast cancer.Notably,the proportion of MDSCs decreased,whereas CD8? T cell infiltration in-creased significantly,with the more pronounced effect observed in the Alpelisib@MSPM treatment group.Conclusions:PIK3CA mutations drive the formation of a tumor immunosuppressive microenvironment in Luminal breast cancer.Targeted Alpelisib delivery via pH-respons-ive polymer micelles significantly enhances therapeutic efficacy in PIK3CA-mutated breast cancer.
