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Browsing by Author "Yang, Liuqing"
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Item Identification of Hypoxia-ALCAMhigh Macrophage- Exhausted T Cell Axis in Tumor Microenvironment Remodeling for Immunotherapy Resistance(Wiley, 2024) Xun, Zhenzhen; Zhou, Huanran; Shen, Mingyi; Liu, Yao; Sun, Chengcao; Du, Yanhua; Jiang, Zhou; Yang, Liuqing; Zhang, Qing; Lin, Chunru; Hu, Qingsong; Ye, Youqiong; Han, Leng; Biostatistics and Health Data Science, School of MedicineAlthough hypoxia is known to be associated with immune resistance, the adaptability to hypoxia by different cell populations in the tumor microenvironment and the underlying mechanisms remain elusive. This knowledge gap has hindered the development of therapeutic strategies to overcome tumor immune resistance induced by hypoxia. Here, bulk, single‐cell, and spatial transcriptomics are integrated to characterize hypoxia associated with immune escape during carcinogenesis and reveal a hypoxia‐based intercellular communication hub consisting of malignant cells, ALCAM high macrophages, and exhausted CD8+ T cells around the tumor boundary. A hypoxic microenvironment promotes binding of HIF‐1α complex is demonstrated to the ALCAM promoter therefore increasing its expression in macrophages, and the ALCAM high macrophages co‐localize with exhausted CD8+ T cells in the tumor spatial microenvironment and promote T cell exhaustion. Preclinically, HIF‐1ɑ inhibition reduces ALCAM expression in macrophages and exhausted CD8+ T cells and potentiates T cell antitumor function to enhance immunotherapy efficacy. This study reveals the systematic landscape of hypoxia at single‐cell resolution and spatial architecture and highlights the effect of hypoxia on immunotherapy resistance through the ALCAM high macrophage‐exhausted T cell axis, providing a novel immunotherapeutic strategy to overcome hypoxia‐induced resistance in cancers.Item Single-nucleotide polymorphisms are associated with cognitive decline at Alzheimer's disease conversion within mild cognitive impairment patients(Elsevier, 2017-04-23) Lee, Eunjee; Giovanello, Kelly S.; Saykin, Andrew J.; Xie, Fengchang; Kong, Dehan; Wang, Yue; Yang, Liuqing; Ibrahim, Joseph G.; Doraiswamy, P. Murali; Zhu, Hongtu; Department of Radiology and Imaging Sciences, IU School of MedicineINTRODUCTION: The growing public threat of Alzheimer's disease (AD) has raised the urgency to quantify the degree of cognitive decline during the conversion process of mild cognitive impairment (MCI) to AD and its underlying genetic pathway. The aim of this article was to test genetic common variants associated with accelerated cognitive decline after the conversion of MCI to AD. METHODS: In 583 subjects with MCI enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI; ADNI-1, ADNI-Go, and ADNI-2), 245 MCI participants converted to AD at follow-up. We tested the interaction effects between individual single-nucleotide polymorphisms and AD diagnosis trajectory on the longitudinal Alzheimer's Disease Assessment Scale-Cognition scores. RESULTS: Our findings reveal six genes, including BDH1, ST6GAL1, RAB20, PDS5B, ADARB2, and SPSB1, which are directly or indirectly related to MCI conversion to AD. DISCUSSION: This genome-wide association study sheds light on a genetic mechanism of longitudinal cognitive changes during the transition period from MCI to AD.