Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to Immunotherapy
Abstract The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and activates the unfolded protein response (UPR). As an adaptive cellular response to hostile microenvironments, such as hypoxia, nutrient deprivation, oxidative stress, and chemotherapeut...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-023-01438-0 |
| _version_ | 1797273797262311424 |
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| author | Jiang He You Zhou Lunquan Sun |
| author_facet | Jiang He You Zhou Lunquan Sun |
| author_sort | Jiang He |
| collection | DOAJ |
| description | Abstract The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and activates the unfolded protein response (UPR). As an adaptive cellular response to hostile microenvironments, such as hypoxia, nutrient deprivation, oxidative stress, and chemotherapeutic drugs, the UPR is activated in diverse cancer types and functions as a dynamic tumour promoter in cancer development; this role of the UPR indicates that regulation of the UPR can be utilized as a target for tumour treatment. T-cell exhaustion mainly refers to effector T cells losing their effector functions and expressing inhibitory receptors, leading to tumour immune evasion and the loss of tumour control. Emerging evidence suggests that the UPR plays a crucial role in T-cell exhaustion, immune evasion, and resistance to immunotherapy. In this review, we summarize the molecular basis of UPR activation, the effect of the UPR on immune evasion, the emerging mechanisms of the UPR in chemotherapy and immunotherapy resistance, and agents that target the UPR for tumour therapeutics. An understanding of the role of the UPR in immune evasion and therapeutic resistance will be helpful to identify new therapeutic modalities for cancer treatment. Video Abstract |
| first_indexed | 2024-03-07T14:49:21Z |
| format | Article |
| id | doaj.art-22829611bebf400b8ca43e79f1703251 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-03-07T14:49:21Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-22829611bebf400b8ca43e79f17032512024-03-05T19:46:41ZengBMCCell Communication and Signaling1478-811X2024-01-0122112210.1186/s12964-023-01438-0Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to ImmunotherapyJiang He0You Zhou1Lunquan Sun2Xiangya Cancer Center, Xiangya Hospital, Central South UniversityDepartment of Pathology, Tongji Medical College Union Hospital, Huazhong University of Science and TechnologyXiangya Cancer Center, Xiangya Hospital, Central South UniversityAbstract The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and activates the unfolded protein response (UPR). As an adaptive cellular response to hostile microenvironments, such as hypoxia, nutrient deprivation, oxidative stress, and chemotherapeutic drugs, the UPR is activated in diverse cancer types and functions as a dynamic tumour promoter in cancer development; this role of the UPR indicates that regulation of the UPR can be utilized as a target for tumour treatment. T-cell exhaustion mainly refers to effector T cells losing their effector functions and expressing inhibitory receptors, leading to tumour immune evasion and the loss of tumour control. Emerging evidence suggests that the UPR plays a crucial role in T-cell exhaustion, immune evasion, and resistance to immunotherapy. In this review, we summarize the molecular basis of UPR activation, the effect of the UPR on immune evasion, the emerging mechanisms of the UPR in chemotherapy and immunotherapy resistance, and agents that target the UPR for tumour therapeutics. An understanding of the role of the UPR in immune evasion and therapeutic resistance will be helpful to identify new therapeutic modalities for cancer treatment. Video Abstracthttps://doi.org/10.1186/s12964-023-01438-0Unfolded protein responseT-cell exhaustionImmune checkpoint therapyChemotherapy |
| spellingShingle | Jiang He You Zhou Lunquan Sun Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to Immunotherapy Cell Communication and Signaling Unfolded protein response T-cell exhaustion Immune checkpoint therapy Chemotherapy |
| title | Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to Immunotherapy |
| title_full | Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to Immunotherapy |
| title_fullStr | Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to Immunotherapy |
| title_full_unstemmed | Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to Immunotherapy |
| title_short | Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to Immunotherapy |
| title_sort | emerging mechanisms of the unfolded protein response in therapeutic resistance from chemotherapy to immunotherapy |
| topic | Unfolded protein response T-cell exhaustion Immune checkpoint therapy Chemotherapy |
| url | https://doi.org/10.1186/s12964-023-01438-0 |
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