Browsing by Subject "Tumor Microenvironment"

Now showing 1 - 3 of 3
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    The microenvironment matters: estrogen deficiency fuels cancer bone metastases
    (American Association for Cancer Research, 2014-06-01) Wright, Laura E.; Guise, Theresa A.; Department of Medicine, IU School of Medicine
    Factors released during osteoclastic bone resorption enhance disseminated breast cancer cell progression by stimulating invasiveness, growth, and a bone-resorptive phenotype in cancer cells. Postmenopausal bone loss may accelerate progression of breast cancer growth in bone, explaining the anticancer benefit of the bone-specific antiresorptive agent zoledronic acid in the postmenopausal setting. Clin Cancer Res; 20(11); 2817-9. ©2014 AACR.
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    Systemic immune-inflammation index in germ-cell tumours: search for a biological prognostic biomarker
    (Springer Nature, 2018-03-20) Albany, Costantine; Medicine, School of Medicine
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    Targeting the chromatin effector Pygo2 promotes cytotoxic T cell responses and overcomes immunotherapy resistance in prostate cancer
    (American Association for the Advancement of Science, 2023) Zhu, Yini; Zhao, Yun; Wen, Jiling; Liu, Sheng; Huang, Tianhe; Hatial, Ishita; Peng, Xiaoxia; Al Janabi, Hawraa; Huang, Gang; Mittlesteadt, Jackson; Cheng, Michael; Bhardwaj, Atul; Ashfeld, Brandon L.; Kao, Kenneth R.; Maeda, Dean Y.; Dai, Xing; Wiest, Olaf; Blagg, Brian S. J.; Lu, Xuemin; Cheng, Liang; Wan, Jun; Lu, Xin; Medical and Molecular Genetics, School of Medicine
    The noninflamed microenvironment in prostate cancer represents a barrier to immunotherapy. Genetic alterations underlying cancer cell-intrinsic oncogenic signaling are increasingly appreciated for their role in shaping the immune landscape. Recently, we identified Pygopus 2 (PYGO2) as the driver oncogene for the amplicon at 1q21.3 in prostate cancer. Here, using transgenic mouse models of metastatic prostate adenocarcinoma, we found that Pygo2 deletion decelerated tumor progression, diminished metastases, and extended survival. Pygo2 loss augmented the activation and infiltration of cytotoxic T lymphocytes (CTLs) and sensitized tumor cells to T cell killing. Mechanistically, Pygo2 orchestrated a p53/Sp1/Kit/Ido1 signaling network to foster a microenvironment hostile to CTLs. Genetic or pharmacological inhibition of Pygo2 enhanced the antitumor efficacy of immunotherapies using immune checkpoint blockade (ICB), adoptive cell transfer, or agents inhibiting myeloid-derived suppressor cells. In human prostate cancer samples, Pygo2 expression was inversely correlated with the infiltration of CD8+ T cells. Analysis of the ICB clinical data showed association between high PYGO2 level and worse outcome. Together, our results highlight a potential path to improve immunotherapy using Pygo2-targeted therapy for advanced prostate cancer.