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4 "Tumor immunity"
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Review Article
Role of HIF-1α in the Responses of Tumors to Radiotherapy and Chemotherapy
Chang W Song, Hyunkyung Kim, Mi-Sook Kim, Heon J Park, Sun-Ha Paek, Stephanie Terezakis, L Chinsoo Cho
Cancer Res Treat. 2025;57(1):1-10.   Published online June 5, 2024
DOI: https://doi.org/10.4143/crt.2024.255
AbstractAbstract PDFPubReaderePub
Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.
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Original Articles
Gastrointestinal cancer
Molecular and Immune Profiling of Syngeneic Mouse Models Predict Response to Immune Checkpoint Inhibitors in Gastric Cancer
Dagyeong Lee, Junyong Choi, Hye Jeong Oh, In-Hye Ham, Sung Hak Lee, Sachiyo Nomura, Sang-Uk Han, Hoon Hur
Cancer Res Treat. 2023;55(1):167-178.   Published online May 20, 2022
DOI: https://doi.org/10.4143/crt.2022.094
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Appropriate preclinical mouse models are needed to evaluate the response to immunotherapeutic agents. Immunocompetent mouse models have rarely been reported for gastric cancer. Thus, we investigated immunophenotypes and responses to immune checkpoint inhibitor (ICI) in immunocompetent mouse models using various murine gastric cancer cell lines.
Materials and Methods
We constructed subcutaneous syngeneic tumors with murine gastric cancer cell lines, YTN3 and YTN16, in C57BL/6J mice. Mice were intraperitoneally treated with IgG isotype control or an anti–programmed death-ligand 1 (PD-L1) neutralizing antibody. We used immunohistochemistry to evaluate the tumor-infiltrating immune cells of formalin-fixed paraffin-embedded mouse tumor tissues. We compared the protein and RNA expression between YTN3 and YTN16 cell lines using a mouse cytokine array and RNA sequencing.
Results
The mouse tumors revealed distinct histological and molecular characteristics. YTN16 cells showed upregulation of genes and proteins related to immunosuppression, such as Ccl2 (CCL2) and Csf1 (M-CSF). Macrophages and exhausted T cells were more enriched in YTN16 tumors than in YTN3 tumors. Several YTN3 tumors were completely regressed by the PD-L1 inhibitor, whereas YTN16 tumors were unaffected. Although treatment with a PD-L1 inhibitor increased infiltration of T cells in both the tumors, the proportion of exhausted immune cells did not decrease in the non-responder group.
Conclusion
We confirmed the histological and molecular features of cancer cells with various responses to ICI. Our models can be used in preclinical research on ICI resistance mechanisms to enhance clinical efficacy.

Citations

Citations to this article as recorded by  
  • Tubulointerstitial nephritis antigen-like 1 from cancer-associated fibroblasts contribute to the progression of diffuse-type gastric cancers through the interaction with integrin β1
    Dagyeong Lee, In-Hye Ham, Hye Jeong Oh, Dong Min Lee, Jung Hwan Yoon, Sang-Yong Son, Tae-Min Kim, Jae-Young Kim, Sang-Uk Han, Hoon Hur
    Journal of Translational Medicine.2024;[Epub]     CrossRef
  • Safety and Efficacy of Neoadjuvant Chemoimmunotherapy in Gastric Cancer Patients with a PD-L1 Positive Status: A Case Report
    Alexandra V. Avgustinovich, Olga V. Bakina, Sergey G. Afanas’ev, Liudmila V. Spirina, Alexander M. Volkov
    Current Issues in Molecular Biology.2023; 45(9): 7642.     CrossRef
  • Targeting GAS6/AXL signaling improves the response to immunotherapy by restoring the anti-immunogenic tumor microenvironment in gastric cancer
    Tae Hoon Kim, Dagyeong Lee, Hye Jeong Oh, In-Hye Ham, Dong Min Lee, Yulim Lee, Zhang Zhang, Ding Ke, Hoon Hur
    Life Sciences.2023; 335: 122230.     CrossRef
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T Cells Modified with CD70 as an Alternative Cellular Vaccine for Antitumor Immunity
Sang-Eun Lee, A-Ri Shin, Hyun-Jung Sohn, Hyun-Il Cho, Tai-Gyu Kim
Cancer Res Treat. 2020;52(3):747-763.   Published online February 14, 2020
DOI: https://doi.org/10.4143/crt.2019.721
AbstractAbstract PDFPubReaderePub
Purpose
Successful tumor eradication primarily depends on generation and maintenance of a large population of tumor-reactive CD8 T cells. Dendritic cells (DCs) are well-known potent antigen-presenting cells and have applied to clinics as potent antitumor therapeutic agents. However, high cost and difficulty in obtaining sufficient amounts for clinical use are the crucial drawbacks of DC-based vaccines. Here, we aimed to develop T cell–based vaccine capable of eliciting potent antitumor therapeutic effects by providing effective costimulatory signals.
Materials and Methods
Antigenic peptide-loaded T cells transfected with retrovirus encoding costimulatory ligands CD70, CD80, OX40L, or 4-1BBL were assessed for antigen-specific CD8 T-cell responses and evaluated antitumor effects along with immunization of a mixture of synthetic peptides, poly-IC and anti-CD40 antibodies (TriVax).
Results
T cells expressing CD70 (CD70-T) exhibited similar level of stimulatory functionality and therapeutic efficacy as DCs. Moreover, CD70-T prime followed by TriVax booster heterologous vaccination elicited therapeutic antitumor effect against B16 melanoma where mediated by CD8 T cells but not CD4 T cells or natural killer cells. The combination with programmed death-ligand 1 blockade led to potent therapeutic efficacy which exhibited increased tumor-infiltrating CD8 T cells. CD70-T pulsed with multi-antigenic peptide generated multiple antigen-specific polyvalent CD8 T cells that were capable of inhibiting tumor growth effectively. Moreover, CD70-T vaccination resulted in higher expansion and migration of adoptively transferred T cells into tumor sites and elicits enhanced therapeutic effects with peptide-based booster immu-nization.
Conclusion
These results imply that T cells endowed with CD70 enable the design of effective vaccination strategies against solid cancer, which may overcome current limitations of DC-based vaccines.

Citations

Citations to this article as recorded by  
  • Unveiling the role of MDH1 in breast cancer drug resistance through single-cell sequencing and schottenol intervention
    Jian Lu, Feng Ding, Yongjie Sun, Yu Zhao, Wenbiao Ma, Huan Zhang, Bo Shi
    Cellular Signalling.2025; 127: 111608.     CrossRef
  • Amplifying mRNA vaccines: potential versatile magicians for oncotherapy
    Chaoying Hu, Jianyang Liu, Feiran Cheng, Yu Bai, Qunying Mao, Miao Xu, Zhenglun Liang
    Frontiers in Immunology.2023;[Epub]     CrossRef
  • STING activation normalizes the intraperitoneal vascular-immune microenvironment and suppresses peritoneal carcinomatosis of colon cancer
    Seung Joon Lee, Hannah Yang, Woo Ram Kim, Yu Seong Lee, Won Suk Lee, So Jung Kong, Hye Jin Lee, Jeong Hun Kim, Jaekyung Cheon, Beodeul Kang, Hong Jae Chon, Chan Kim
    Journal for ImmunoTherapy of Cancer.2021; 9(6): e002195.     CrossRef
  • Comprehensive Analysis of the Prognostic Value and Immune Function of Immune Checkpoints in Stomach Adenocarcinoma
    Kai Shen, Tong Liu
    International Journal of General Medicine.2021; Volume 14: 5807.     CrossRef
  • 9,165 View
  • 288 Download
  • 3 Web of Science
  • 4 Crossref
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Review Article
RNA Regulation in Neurologic Disease and Cancer
Robert B. Darnell
Cancer Res Treat. 2010;42(3):125-129.   Published online September 30, 2010
DOI: https://doi.org/10.4143/crt.2010.42.3.125
AbstractAbstract PDFPubReaderePub

The paraneoplastic neurologic diseases (PNDs) are brain degenerations that develop in the setting of clinically inapparent cancers. PNDs arise when common cancers express brain proteins, triggering an anti-tumor immune response and tumor immunity. Research on these brain-cancer proteins has revealed a new world of neuron-specific RNA binding proteins whose functions may be aberrantly used by tumor cells. Efforts to gain insight into their function has led to the development of new methods and strategies to understand RNA protein regulation in living tissues.

Citations

Citations to this article as recorded by  
  • Identifying the mitochondrial ribosomal protein MRPL13 as an oncogenic RBP that promotes proliferation, migration, and anti-apoptotic effects in esophageal cancer cells
    Yaxi Song, Hui Wang, Shiyao Li, Weili Tao, Chunqing Li, Bin Wang, Caifeng Gong
    Heliyon.2024; : e39546.     CrossRef
  • LARP6 suppresses colorectal cancer progression through ZNF267/SGMS2-mediated imbalance of sphingomyelin synthesis
    Xiaoli Long, Xunhua Liu, Ting Deng, Jianxiong Chen, Jiawen Lan, Sijing Zhang, Miao Zhou, Dan Guo, Jun Zhou
    Journal of Experimental & Clinical Cancer Research.2023;[Epub]     CrossRef
  • Effect and mechanism of circRNAs in tumor angiogenesis and clinical application
    Luyang Zhao, Yuying Guo, Yaxin Guo, Xiang Ji, Dandan Fan, Chen Chen, Weitang Yuan, Zhenqiang Sun, Zhenyu Ji
    International Journal of Cancer.2022; 150(8): 1223.     CrossRef
  • Widespread autogenous mRNA–protein interactions detected by CLIP-seq
    Thomas H Kapral, Fiona Farnhammer, Weihao Zhao, Zhi J Lu, Bojan Zagrovic
    Nucleic Acids Research.2022; 50(17): 9984.     CrossRef
  • Computational tools to study RNA-protein complexes
    Sneha Bheemireddy, Sankaran Sandhya, Narayanaswamy Srinivasan, Ramanathan Sowdhamini
    Frontiers in Molecular Biosciences.2022;[Epub]     CrossRef
  • RNA Regulators in Leukemia and Lymphoma
    Camila Prieto, Michael G. Kharas
    Cold Spring Harbor Perspectives in Medicine.2020; 10(5): a034967.     CrossRef
  • Diverse roles of RNA‐binding proteins in cancer traits and their implications in gastrointestinal cancers
    Kiyoshi Masuda, Yuki Kuwano
    WIREs RNA.2019;[Epub]     CrossRef
  • MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change
    Qianru He, Lini Zhao, Xiaobai Liu, Jian Zheng, Yunhui Liu, Libo Liu, Jun Ma, Heng Cai, Zhen Li, Yixue Xue
    Journal of Experimental & Clinical Cancer Research.2019;[Epub]     CrossRef
  • KHDRBS3 regulates the permeability of blood–tumor barrier via cDENND4C/miR-577 axis
    Peiqi Wu, Yang Gao, Shuyuan Shen, Yixue Xue, Xiaobai Liu, Xuelei Ruan, Lianqi Shao, Yunhui Liu, Ping Wang
    Cell Death & Disease.2019;[Epub]     CrossRef
  • IDH1 fine-tunes cap-dependent translation initiation
    Lichao Liu, J Yuyang Lu, Fajin Li, Xudong Xing, Tong Li, Xuerui Yang, Xiaohua Shen, Zefeng Wang
    Journal of Molecular Cell Biology.2019; 11(10): 816.     CrossRef
  • Expanding horizons: new roles for non-canonical RNA-binding proteins in cancer
    Samantha Moore, Aino I Järvelin, Ilan Davis, Gareth L Bond, Alfredo Castello
    Current Opinion in Genetics & Development.2018; 48: 112.     CrossRef
  • Graphene Oxide-Facilitated Comprehensive Analysis of Cellular Nucleic Acid Binding Proteins for Lung Cancer
    Zhi Shang, Liqiang Qian, Sha Liu, Xiaomin Niu, Zhi Qiao, Yan Sun, Yan Zhang, Liu-Yin Fan, Xin Guan, Cheng-Xi Cao, Hua Xiao
    ACS Applied Materials & Interfaces.2018; 10(21): 17756.     CrossRef
  • NOVA1 regulates hTERT splicing and cell growth in non-small cell lung cancer
    Andrew T. Ludlow, Mandy Sze Wong, Jerome D. Robin, Kimberly Batten, Laura Yuan, Tsung-Po Lai, Nicole Dahlson, Lu Zhang, Ilgen Mender, Enzo Tedone, Mohammed E. Sayed, Woodring E. Wright, Jerry W. Shay
    Nature Communications.2018;[Epub]     CrossRef
  • Identification and Analysis of Key Residues in Protein–RNA Complexes
    A. Kulandaisamy, Ambuj Srivastava, Pradeep Kumar, R. Nagarajan, S. Binny Priya, M. Michael Gromiha
    IEEE/ACM Transactions on Computational Biology and Bioinformatics.2018; 15(5): 1436.     CrossRef
  • RNA Binding Protein as an Emerging Therapeutic Target for Cancer Prevention and Treatment
    Suntaek Hong
    Journal of Cancer Prevention.2017; 22(4): 203.     CrossRef
  • The expanding universe of ribonucleoproteins: of novel RNA-binding proteins and unconventional interactions
    Benedikt M. Beckmann, Alfredo Castello, Jan Medenbach
    Pflügers Archiv - European Journal of Physiology.2016; 468(6): 1029.     CrossRef
  • NOVA2-mediated RNA regulation is required for axonal pathfinding during development
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    Nucleic Acids Research.2016; : gkw803.     CrossRef
  • UNR/CSDE1 Drives a Post-transcriptional Program to Promote Melanoma Invasion and Metastasis
    Laurence Wurth, Panagiotis Papasaikas, David Olmeda, Nadine Bley, Guadalupe T. Calvo, Santiago Guerrero, Daniela Cerezo-Wallis, Javier Martinez-Useros, María García-Fernández, Stefan Hüttelmaier, Maria S. Soengas, Fátima Gebauer
    Cancer Cell.2016; 30(5): 694.     CrossRef
  • Tumor-promoting function and prognostic significance of the RNA-binding protein T-cell intracellular antigen-1 in esophageal squamous cell carcinoma
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    Oncotarget.2016; 7(13): 17111.     CrossRef
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    Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms.2015; 1849(7): 881.     CrossRef
  • RNA-binding proteins in neurological diseases
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    Science China Life Sciences.2014; 57(4): 432.     CrossRef
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    Trends in Genetics.2013; 29(5): 318.     CrossRef
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