DLL4-targeted CAR-T therapy sensitizes neoadjuvant chemotherapy via eliminating cancer stem cells and reshaping immune microenvironment in HER2+breast cancer DOI Creative Commons

Jingrui Yan,

Yongjie Xie,

Ziyun Liu

и другие.

Journal for ImmunoTherapy of Cancer, Год журнала: 2024, Номер 12(11), С. e009636 - e009636

Опубликована: Ноя. 1, 2024

Background Neoadjuvant therapy with trastuzumab, pertuzumab and paclitaxel (THP) has significantly improved the prognosis of patients human epidermal growth factor receptor 2 (HER2) + breast cancer (BC). However, there remains a subset non-responsive patients. Thus, this study sought to identify key regulators THP neoadjuvant resistance potential targets sensitize sensitivity. Methods The Cancer Genome Atlas database, Gene Expression Omnibus membrane protein database were used regulator resistance. biological functions mechanisms delta-like 4 proteins (DLL4) in investigated vitro vivo using bioinformatic analysis, multiplex immunofluorescence, flow cytometry, sphere formation assays chromatin immunoprecipitation, etc. Furthermore, DLL4-targeted chimeric antigen (CAR)-T cells established therapy. Results DLL4 was identified as target for HER2 BC. Mechanistically, tumor exhibited enhanced stemness chemotherapy. Additionally, soluble can split away from diffuse into stroma, where it activate Notch signaling pathway neutrophils, inducing release neutrophil extracellular traps (NETs) by regulating transcription MPO, PDIA4 ELANE. This led exclusion lymphocyte infiltration, thereby enhancing What is more, we designed CAR-T eliminate reverse resistant status. Conclusions Our revealed novel cell immune including NET T exclusion, which collectively contributed provided CAR-T-based

Язык: Английский

Cancer stem cell-derived exosomes in CD8+ T cell exhaustion DOI
Amir Gholami

International Immunopharmacology, Год журнала: 2024, Номер 137, С. 112509 - 112509

Опубликована: Июнь 18, 2024

Язык: Английский

Процитировано

5
Antitumor Research Based on Drug Delivery Carriers: Reversing the Polarization of Tumor-Associated Macrophages DOI
Xinyu Cao,

Shen Wan,

Bingyu Wu

и другие.

Molecular Pharmaceutics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 27, 2025

The development of malignant tumors is a complex process that involves the tumor microenvironment (TME). An immunosuppressive TME presents significant challenges to current cancer therapies, serving as key mechanism through which cells evade immune detection and play crucial role in progression metastasis. This impedes optimal effectiveness immunotherapeutic approaches, including cytokines, checkpoint inhibitors, vaccines. Tumor-associated macrophages (TAMs), major component tumor-infiltrating cells, exhibit dual functionalities: M1-like TAMs suppress tumorigenesis, while M2-like promote growth Consequently, various nanocarriers aimed at polarizing phenotypes distinct mechanisms has emerged promising therapeutic strategy inhibit escape enhance antitumor responses. Review covers origin types TAMs, common pathways regulating macrophage polarization, progression, strategies targeting aiming provide comprehensive understanding guidance for future research clinical applications.

Язык: Английский

Процитировано

0
DLL4-targeted CAR-T therapy sensitizes neoadjuvant chemotherapy via eliminating cancer stem cells and reshaping immune microenvironment in HER2+breast cancer DOI Creative Commons

Jingrui Yan,

Yongjie Xie,

Ziyun Liu

и другие.

Journal for ImmunoTherapy of Cancer, Год журнала: 2024, Номер 12(11), С. e009636 - e009636

Опубликована: Ноя. 1, 2024

Background Neoadjuvant therapy with trastuzumab, pertuzumab and paclitaxel (THP) has significantly improved the prognosis of patients human epidermal growth factor receptor 2 (HER2) + breast cancer (BC). However, there remains a subset non-responsive patients. Thus, this study sought to identify key regulators THP neoadjuvant resistance potential targets sensitize sensitivity. Methods The Cancer Genome Atlas database, Gene Expression Omnibus membrane protein database were used regulator resistance. biological functions mechanisms delta-like 4 proteins (DLL4) in investigated vitro vivo using bioinformatic analysis, multiplex immunofluorescence, flow cytometry, sphere formation assays chromatin immunoprecipitation, etc. Furthermore, DLL4-targeted chimeric antigen (CAR)-T cells established therapy. Results DLL4 was identified as target for HER2 BC. Mechanistically, tumor exhibited enhanced stemness chemotherapy. Additionally, soluble can split away from diffuse into stroma, where it activate Notch signaling pathway neutrophils, inducing release neutrophil extracellular traps (NETs) by regulating transcription MPO, PDIA4 ELANE. This led exclusion lymphocyte infiltration, thereby enhancing What is more, we designed CAR-T eliminate reverse resistant status. Conclusions Our revealed novel cell immune including NET T exclusion, which collectively contributed provided CAR-T-based

Язык: Английский

Процитировано

2