NK cells and solid tumors: therapeutic potential and persisting obstacles
Abstract Natural killer (NK) cells, which are innate lymphocytes endowed with potent cytotoxic activity, have recently attracted attention as potential anticancer therapeutics. While NK cells mediate encouraging responses in patients with leukemia, the therapeutic effects of NK cell infusion in pati...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-11-01
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| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12943-022-01672-z |
| _version_ | 1811223521500594176 |
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| author | Le Tong Carlos Jiménez-Cortegana Apple H.M. Tay Stina Wickström Lorenzo Galluzzi Andreas Lundqvist |
| author_facet | Le Tong Carlos Jiménez-Cortegana Apple H.M. Tay Stina Wickström Lorenzo Galluzzi Andreas Lundqvist |
| author_sort | Le Tong |
| collection | DOAJ |
| description | Abstract Natural killer (NK) cells, which are innate lymphocytes endowed with potent cytotoxic activity, have recently attracted attention as potential anticancer therapeutics. While NK cells mediate encouraging responses in patients with leukemia, the therapeutic effects of NK cell infusion in patients with solid tumors are limited. Preclinical and clinical data suggest that the efficacy of NK cell infusion against solid malignancies is hampered by several factors including inadequate tumor infiltration and persistence/activation in the tumor microenvironment (TME). A number of metabolic features of the TME including hypoxia as well as elevated levels of adenosine, reactive oxygen species, and prostaglandins negatively affect NK cell activity. Moreover, cancer-associated fibroblasts, tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells actively suppress NK cell-dependent anticancer immunity. Here, we review the metabolic and cellular barriers that inhibit NK cells in solid neoplasms as we discuss potential strategies to circumvent such obstacles towards superior therapeutic activity. |
| first_indexed | 2024-04-12T08:34:05Z |
| format | Article |
| id | doaj.art-79fefdad892946759dec98503965999f |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-04-12T08:34:05Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-79fefdad892946759dec98503965999f2022-12-22T03:40:03ZengBMCMolecular Cancer1476-45982022-11-0121111810.1186/s12943-022-01672-zNK cells and solid tumors: therapeutic potential and persisting obstaclesLe Tong0Carlos Jiménez-Cortegana1Apple H.M. Tay2Stina Wickström3Lorenzo Galluzzi4Andreas Lundqvist5Department of Oncology-Pathology, Karolinska InstituteDepartment of Radiation Oncology, Weill Cornell Medical CollegeDepartment of Oncology-Pathology, Karolinska InstituteDepartment of Oncology-Pathology, Karolinska InstituteDepartment of Radiation Oncology, Weill Cornell Medical CollegeDepartment of Oncology-Pathology, Karolinska InstituteAbstract Natural killer (NK) cells, which are innate lymphocytes endowed with potent cytotoxic activity, have recently attracted attention as potential anticancer therapeutics. While NK cells mediate encouraging responses in patients with leukemia, the therapeutic effects of NK cell infusion in patients with solid tumors are limited. Preclinical and clinical data suggest that the efficacy of NK cell infusion against solid malignancies is hampered by several factors including inadequate tumor infiltration and persistence/activation in the tumor microenvironment (TME). A number of metabolic features of the TME including hypoxia as well as elevated levels of adenosine, reactive oxygen species, and prostaglandins negatively affect NK cell activity. Moreover, cancer-associated fibroblasts, tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells actively suppress NK cell-dependent anticancer immunity. Here, we review the metabolic and cellular barriers that inhibit NK cells in solid neoplasms as we discuss potential strategies to circumvent such obstacles towards superior therapeutic activity.https://doi.org/10.1186/s12943-022-01672-zAdoptive cell therapyCAR T cellsCGAS/STING1 signalingImmune checkpoint inhibitorsPD-L1TREG cells |
| spellingShingle | Le Tong Carlos Jiménez-Cortegana Apple H.M. Tay Stina Wickström Lorenzo Galluzzi Andreas Lundqvist NK cells and solid tumors: therapeutic potential and persisting obstacles Molecular Cancer Adoptive cell therapy CAR T cells CGAS/STING1 signaling Immune checkpoint inhibitors PD-L1 TREG cells |
| title | NK cells and solid tumors: therapeutic potential and persisting obstacles |
| title_full | NK cells and solid tumors: therapeutic potential and persisting obstacles |
| title_fullStr | NK cells and solid tumors: therapeutic potential and persisting obstacles |
| title_full_unstemmed | NK cells and solid tumors: therapeutic potential and persisting obstacles |
| title_short | NK cells and solid tumors: therapeutic potential and persisting obstacles |
| title_sort | nk cells and solid tumors therapeutic potential and persisting obstacles |
| topic | Adoptive cell therapy CAR T cells CGAS/STING1 signaling Immune checkpoint inhibitors PD-L1 TREG cells |
| url | https://doi.org/10.1186/s12943-022-01672-z |
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