年間 6 号発行
ISSN 印刷: 1040-8401
ISSN オンライン: 2162-6472
Indexed in
Tumor Hypoxia: A Key Determinant of Microenvironment Hostility and a Major Checkpoint during the Antitumor Response
要約
Recent antitumor immunotherapies such as monoclonal antibodies targeting immune checkpoints have led to outstanding results in several cancers. However, despite the favorable outcomes for responding patients, the response rate remains relatively low. This is in part due to the influence of the tumor microenvironment (TME) in protecting the tumor from the antitumor immune response and facilitating immune escape. Tumor hypoxia is one of the most important features of the TME, exerting an adverse effect on tumor aggressiveness and patient prognosis. Hypoxic stress interferes with immune plasticity and promotes tumor heterogeneity and progression. Cellular adaptation to hypoxia is primarily mediated by a family of transcriptional regulators, hypoxia-inducible factor (HIF). Apart from hypoxia, the HIF pathway is modulated in a hypoxia-independent manner. HIF-1α stabilization and activity are regulated by epigenetic changes and mutations. Strong evidence indicates that tumor hypoxia controls malignant and metastatic phenotype of cancer cells and therefore presents a unique therapeutic challenge in the treatment of solid malignancies. An alluring alternative strategy to reinvigorate anticancer immune responses comes from the emerging field of TME and its associated pathways. Targeting hypoxia or its associated pathways may therefore offer new options in the design of innovative cancer immunotherapy approaches. In this article, we briefly review the potential of hypoxic stress on tumor plasticity and stromal reactivity as well as the possible targeting of hypoxia-induced pathways to increase immunotherapy efficiency.
-
Baxevanis Constantin N., Fortis Sotirios P., Perez Sonia A., The balance between breast cancer and the immune system: Challenges for prognosis and clinical benefit from immunotherapies, Seminars in Cancer Biology, 72, 2021. Crossref
-
Moldogazieva Nurbubu T., Mokhosoev Innokenty M., Terentiev Alexander A., Metabolic Heterogeneity of Cancer Cells: An Interplay between HIF-1, GLUTs, and AMPK, Cancers, 12, 4, 2020. Crossref
-
Abou Khouzam Raefa, Goutham Hassan Venkatesh, Zaarour Rania Faouzi, Chamseddine Ali N, Francis Amirtharaj, Buart Stéphanie, Terry Stéphane, Chouaib Salem, Integrating tumor hypoxic stress in novel and more adaptable strategies for cancer immunotherapy, Seminars in Cancer Biology, 65, 2020. Crossref
-
Pang Yan, Zhu Zhide, Wen Zhihao, Lu Junshen, Lin Hao, Tang Meiling, Xu Zhiliang, Lu Jianqi, HIGD‑1B inhibits hypoxia‑induced mitochondrial fragmentation by regulating OPA1 cleavage in cardiomyocytes, Molecular Medicine Reports, 24, 2, 2021. Crossref
-
Wang Bin, Zhao Qin, Zhang Yuyu, Liu Zijing, Zheng Zhuangzhuang, Liu Shiyu, Meng Lingbin, Xin Ying, Jiang Xin, Targeting hypoxia in the tumor microenvironment: a potential strategy to improve cancer immunotherapy, Journal of Experimental & Clinical Cancer Research, 40, 1, 2021. Crossref
-
Xing Shan, Tian Zhi, Zheng Wenying, Yang Wenjuan, Du Nan, Gu Yixue, Yin Jiang, Liu Hao, Jia Xiaoting, Huang Donglan, Liu Wanli, Deng Min, Hypoxia downregulated miR-4521 suppresses gastric carcinoma progression through regulation of IGF2 and FOXM1, Molecular Cancer, 20, 1, 2021. Crossref
-
Abou Khouzam Raefa, Zaarour Rania Faouzi, Brodaczewska Klaudia, Azakir Bilal, Venkatesh Goutham Hassan, Thiery Jerome, Terry Stéphane, Chouaib Salem, The Effect of Hypoxia and Hypoxia-Associated Pathways in the Regulation of Antitumor Response: Friends or Foes?, Frontiers in Immunology, 13, 2022. Crossref
-
Wang Jianlong, Li Tao, Ma Lifeng, Liu Guochao, Wang Guiying, Kang Jiansheng, NDRG2 inhibition facilitates angiogenesis of hepatocellular carcinoma, Open Medicine, 16, 1, 2021. Crossref
-
Wang Shuying, Tan Jin, Miao Yuyang, Zhang Qiang, Mitochondrial Dynamics, Mitophagy, and Mitochondria–Endoplasmic Reticulum Contact Sites Crosstalk Under Hypoxia, Frontiers in Cell and Developmental Biology, 10, 2022. Crossref
-
Ziani Linda, Buart Stéphanie, Chouaib Salem, Thiery Jerome, Hypoxia increases melanoma-associated fibroblasts immunosuppressive potential and inhibitory effect on T cell-mediated cytotoxicity, OncoImmunology, 10, 1, 2021. Crossref
-
Hassan Venkatesh Goutham, Bravo Pamela, Shaaban Moustafa Elsayed Walid, Amirtharaj Francis, Wojtas Bartosz, Abou Khouzam Raefa, Hussein Nawafleh Husam, Mallya Sandeep, Satyamoorthy Kapaettu, Dessen Philippe, Rosselli Filippo, Thiery Jerome, Chouaib Salem, Hypoxia increases mutational load of breast cancer cells through frameshift mutations, OncoImmunology, 9, 1, 2020. Crossref
-
Zhang Fusheng, Liu Haiyang, Duan Meiqi, Wang Guang, Zhang Zhenghou, Wang Yutian, Qian Yiping, Yang Zhi, Jiang Xiaofeng, Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application, Journal of Hematology & Oncology, 15, 1, 2022. Crossref
-
Jin Jianxu, Yu Guiping, Hypoxic lung cancer cell-derived exosomal miR-21 mediates macrophage M2 polarization and promotes cancer cell proliferation through targeting IRF1, World Journal of Surgical Oncology, 20, 1, 2022. Crossref
-
Maulana Tengku Ibrahim, Kromidas Elena, Wallstabe Lars, Cipriano Madalena, Alb Miriam, Zaupa Cécile, Hudecek Michael, Fogal Birgit, Loskill Peter, Immunocompetent cancer-on-chip models to assess immuno-oncology therapy, Advanced Drug Delivery Reviews, 173, 2021. Crossref