NK cell exhaustion in the tumor microenvironment
Natural killer (NK) cells kill mutant cells through death receptors and cytotoxic granules, playing an essential role in controlling cancer progression. However, in the tumor microenvironment (TME), NK cells frequently exhibit an exhausted status, which impairs their immunosurveillance function and...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-11-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1303605/full |
| _version_ | 1797640138609655808 |
|---|---|
| author | Hao Jia Hongmei Yang Huaxing Xiong Kathy Qian Luo Kathy Qian Luo |
| author_facet | Hao Jia Hongmei Yang Huaxing Xiong Kathy Qian Luo Kathy Qian Luo |
| author_sort | Hao Jia |
| collection | DOAJ |
| description | Natural killer (NK) cells kill mutant cells through death receptors and cytotoxic granules, playing an essential role in controlling cancer progression. However, in the tumor microenvironment (TME), NK cells frequently exhibit an exhausted status, which impairs their immunosurveillance function and contributes to tumor immune evasion. Emerging studies are ongoing to reveal the properties and mechanisms of NK cell exhaustion in the TME. In this review, we will briefly introduce the maturation, localization, homeostasis, and cytotoxicity of NK cells. We will then summarize the current understanding of the main mechanisms underlying NK cell exhaustion in the TME in four aspects: dysregulation of inhibitory and activating signaling, tumor cell-derived factors, immunosuppressive cells, and metabolism and exhaustion. We will also discuss the therapeutic approaches currently being developed to reverse NK cell exhaustion and enhance NK cell cytotoxicity in the TME. |
| first_indexed | 2024-03-11T13:26:36Z |
| format | Article |
| id | doaj.art-8da75f7ce7fc4f58891299e39087c00e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T13:26:36Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8da75f7ce7fc4f58891299e39087c00e2023-11-03T06:11:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-11-011410.3389/fimmu.2023.13036051303605NK cell exhaustion in the tumor microenvironmentHao Jia0Hongmei Yang1Huaxing Xiong2Kathy Qian Luo3Kathy Qian Luo4Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, ChinaFaculty of Health Sciences, University of Macau, Taipa, Macao SAR, ChinaFaculty of Health Sciences, University of Macau, Taipa, Macao SAR, ChinaFaculty of Health Sciences, University of Macau, Taipa, Macao SAR, ChinaMinistry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macao SAR, ChinaNatural killer (NK) cells kill mutant cells through death receptors and cytotoxic granules, playing an essential role in controlling cancer progression. However, in the tumor microenvironment (TME), NK cells frequently exhibit an exhausted status, which impairs their immunosurveillance function and contributes to tumor immune evasion. Emerging studies are ongoing to reveal the properties and mechanisms of NK cell exhaustion in the TME. In this review, we will briefly introduce the maturation, localization, homeostasis, and cytotoxicity of NK cells. We will then summarize the current understanding of the main mechanisms underlying NK cell exhaustion in the TME in four aspects: dysregulation of inhibitory and activating signaling, tumor cell-derived factors, immunosuppressive cells, and metabolism and exhaustion. We will also discuss the therapeutic approaches currently being developed to reverse NK cell exhaustion and enhance NK cell cytotoxicity in the TME.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1303605/fullcancertumor microenvironmentNK cellexhaustionimmunotherapy |
| spellingShingle | Hao Jia Hongmei Yang Huaxing Xiong Kathy Qian Luo Kathy Qian Luo NK cell exhaustion in the tumor microenvironment Frontiers in Immunology cancer tumor microenvironment NK cell exhaustion immunotherapy |
| title | NK cell exhaustion in the tumor microenvironment |
| title_full | NK cell exhaustion in the tumor microenvironment |
| title_fullStr | NK cell exhaustion in the tumor microenvironment |
| title_full_unstemmed | NK cell exhaustion in the tumor microenvironment |
| title_short | NK cell exhaustion in the tumor microenvironment |
| title_sort | nk cell exhaustion in the tumor microenvironment |
| topic | cancer tumor microenvironment NK cell exhaustion immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1303605/full |
| work_keys_str_mv | AT haojia nkcellexhaustioninthetumormicroenvironment AT hongmeiyang nkcellexhaustioninthetumormicroenvironment AT huaxingxiong nkcellexhaustioninthetumormicroenvironment AT kathyqianluo nkcellexhaustioninthetumormicroenvironment AT kathyqianluo nkcellexhaustioninthetumormicroenvironment |