Browsing by Subject "Cancer immunity"

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    Rapid Profiling of Tumor-Immune Interaction Using Acoustically Assembled Patient-Derived Cell Clusters
    (Wiley, 2022) Ao, Zheng; Wu, Zhuhao; Cai, Hongwei; Hu, Liya; Li, Xiang; Kaurich, Connor; Chang, Jackson; Gu, Mingxia; Cheng, Liang; Lu, Xin; Guo, Feng; Pathology and Laboratory Medicine, School of Medicine
    Tumor microenvironment crosstalk, in particular interactions between cancer cells, T cells, and myeloid‐derived suppressor cells (MDSCs), mediates tumor initiation, progression, and response to treatment. However, current patient‐derived models such as tumor organoids and 2D cultures lack some essential niche cell types (e.g., MDSCs) and fail to model complex tumor‐immune interactions. Here, the authors present the novel acoustically assembled patient‐derived cell clusters (APCCs) that can preserve original tumor/immune cell compositions, model their interactions in 3D microenvironments, and test the treatment responses of primary tumors in a rapid, scalable, and user‐friendly manner. By incorporating a large array of 3D acoustic trappings within the extracellular matrix, hundreds of APCCs can be assembled within a petri dish within 2 min. Moreover, the APCCs can preserve sensitive and short‐lived (≈1 to 2‐day lifespan in vivo) tumor‐induced MDSCs and model their dynamic suppression of T cell tumor toxicity for up to 24 h. Finally, using the APCCs, the authors succesully model the combinational therapeutic effect of a multi‐kinase inhibitor targeting MDSCs (cabozantinib) and an anti‐PD‐1 immune checkpoint inhibitor (pembrolizumab). The novel APCCs may hold promising potential in predicting treatment response for personalized cancer adjuvant therapy as well as screening novel cancer immunotherapy and combinational therapy.
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    Targeting DDX3X Triggers Antitumor Immunity via a dsRNA-Mediated Tumor-Intrinsic Type I Interferon Response
    (American Association for Cancer Research, 2021) Choi, Hyeongjwa; Kwon, Juntae; Cho, Min Soon; Sun, Yifan; Zheng, Xiaofeng; Wang, Jing; Bouker, Kerrie B.; Casey, John L.; Atkins, Michael B.; Toretsky, Jeffrey; Han, Cecil; Medical and Molecular Genetics, School of Medicine
    Induction of nucleic-acid sensing-mediated type I interferon (IFN) has emerged as a novel approach to activate the immune system against cancer. Here we show that the depletion of DEAD-box RNA helicase 3X (DDX3X) triggers a tumor-intrinsic type I IFN response in breast cancer cells. Depletion or inhibition of DDX3X activity led to aberrant cytoplasmic accumulation of cellular endogenous double-stranded RNAs (dsRNA), which triggered type I IFN production through the melanoma differentiation-associated gene 5 (MDA5)-mediated dsRNA sensing pathway. Furthermore, DDX3X interacted with dsRNA-editing ADAR1 and dual depletion of DDX3X and ADAR1 synergistically activated the cytosolic dsRNA pathway in breast cancer cells. Loss of DDX3X in mouse mammary tumors enhanced anti-tumor activity by increasing the tumor-intrinsic type I IFN response, antigen presentation, and tumor-infiltration of cytotoxic T and dendritic cells. These findings may lead to the development of a novel therapeutic approach for breast cancer by targeting DDX3X in combination with immune checkpoint blockade.