%0 Journal Article
%T Tumors and Their Microenvironment Dual©\Targeting Chemotherapy with Local Immune Adjuvant Therapy for Effective Antitumor Immunity against Breast Cancer
%A Caifeng Deng
%A Jin Zhao
%A Mengdi Jia
%A Quan Zhang
%A Xun Sun
%A Zhirong Zhang
%J Archive of "Advanced Science".
%D 2019
%R 10.1002/advs.201801868
%X Chemotherapy turns tumor cells into ¡°tumor vaccines¡± by immunogenic cell death (ICD). However, it remains a challenge to exploit chemotherapy©\induced ¡°tumor vaccines¡± for solid cancer immunotherapy due to the inefficient effector T cells activation and tumor microenvironment immunosuppression. Here, a matrix metalloprotease 2 responsive liposome (PEG©\FA©\Lip) composed of cleavable PEG chains covering the folate (FA)©\modified liposome is developed to deliver ICD inducer doxorubicin. In breast cancer©\bearing mice, PEG©\FA©\Lip targets both 4T1 breast cancer cells and M2©\tumor associated macrophages (M2©\TAMs) via FA©\receptor mediated endocytosis, resulting in abundant ¡°tumor vaccines¡± and efficient elimination of M2©\TAMs. The combination of local cytosine©\phosphate©\guanine (CpG) therapy facilitates PEG©\FA©\Lip induced ¡°tumor vaccines¡± to effectively arouse systematic effector T cells immune response through promoting dendritic cell maturation and immunostimulatory cytokines secretion. The simultaneous elimination of M2©\TAMs ensures the activated effector T cells exert antitumor immunity within tumor via decreasing immunosuppressive cytokines secretion and tumor infiltration of Treg cells. After receiving the combined treatment, 30.1% of breast cancer©\bearing mice (initial tumor volume > 100 mm3) achieves the goal of tumor eradication. Remarkably, this combination therapy greatly inhibits lung metastasis and controls the growth of already metastasized breast cancers (initial tumor volume > 100 mm3)
%K antitumor immunity
%K chemotherapy©\induced ¡°vaccines¡±
%K effector T cells activation
%K M2©\tumor associated macrophages
%K tumor immunosuppression
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425447/