Functional impact of high extracellular potassium ion on human T-cells
Despite the clinical success of current immunotherapies, there remains a pressing need to fully exploit the power of such treatments and improve their efficacy. Tumor microenvironment (TME) crucially dictates the T-cell anti-tumor immune responses. Yet, individual factors in the TME that drive im...
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| Other Authors: | |
| Format: | Final Year Project (FYP) |
| Language: | English |
| Published: |
Nanyang Technological University
2020
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| Online Access: | https://hdl.handle.net/10356/141847 |
| _version_ | 1811692531790905344 |
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| author | Wong, Brandon Han Siang |
| author2 | Navin Kumar Verma |
| author_facet | Navin Kumar Verma Wong, Brandon Han Siang |
| author_sort | Wong, Brandon Han Siang |
| collection | NTU |
| description | Despite the clinical success of current immunotherapies, there remains a pressing
need to fully exploit the power of such treatments and improve their efficacy. Tumor
microenvironment (TME) crucially dictates the T-cell anti-tumor immune responses.
Yet, individual factors in the TME that drive immune suppression remains to be fully
elucidated. Dying/necrotic tumor cells release a substantial amount of intracellular
potassium ion ([K+]i), increasing extracellular potassium ion ([K+]e) to 5-10 fold. Here,
we investigated the effects of high-[K+]e on the mechanistic and functional aspects of
T-cells. We demonstrated via imaging, real-time impedance-based measurements
and molecular assays that high-[K+]e impedes T-cell motility (15% inhibition) and
possesses a chemotactic influence over T-cells. Moreover, High-[K+]e upregulates
the expression of Kv1.3 K+ channel as well as PD-1 in T-cells. Using Jurkat T-cell line
as a model, we observed that high-[K+]e reduces T-cell cytokines (IL-2 and IFN-𝛾)
production and modulates both AMPK𝛼 and ACC expression and phosphorylation,
which are prerequisite factors in cellular metabolism. Taken together, high-[K+]einduced
impairment of T-cell functions reported in the current study has implications
in T-cell anti-tumor immune responses and immunotherapies. |
| first_indexed | 2024-10-01T06:37:16Z |
| format | Final Year Project (FYP) |
| id | ntu-10356/141847 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:37:16Z |
| publishDate | 2020 |
| publisher | Nanyang Technological University |
| record_format | dspace |
| spelling | ntu-10356/1418472023-02-28T18:07:10Z Functional impact of high extracellular potassium ion on human T-cells Wong, Brandon Han Siang Navin Kumar Verma School of Biological Sciences nkverma@ntu.edu.sg Science::Biological sciences Despite the clinical success of current immunotherapies, there remains a pressing need to fully exploit the power of such treatments and improve their efficacy. Tumor microenvironment (TME) crucially dictates the T-cell anti-tumor immune responses. Yet, individual factors in the TME that drive immune suppression remains to be fully elucidated. Dying/necrotic tumor cells release a substantial amount of intracellular potassium ion ([K+]i), increasing extracellular potassium ion ([K+]e) to 5-10 fold. Here, we investigated the effects of high-[K+]e on the mechanistic and functional aspects of T-cells. We demonstrated via imaging, real-time impedance-based measurements and molecular assays that high-[K+]e impedes T-cell motility (15% inhibition) and possesses a chemotactic influence over T-cells. Moreover, High-[K+]e upregulates the expression of Kv1.3 K+ channel as well as PD-1 in T-cells. Using Jurkat T-cell line as a model, we observed that high-[K+]e reduces T-cell cytokines (IL-2 and IFN-𝛾) production and modulates both AMPK𝛼 and ACC expression and phosphorylation, which are prerequisite factors in cellular metabolism. Taken together, high-[K+]einduced impairment of T-cell functions reported in the current study has implications in T-cell anti-tumor immune responses and immunotherapies. Bachelor of Science in Biological Sciences 2020-06-11T04:13:24Z 2020-06-11T04:13:24Z 2020 Final Year Project (FYP) https://hdl.handle.net/10356/141847 en application/pdf Nanyang Technological University |
| spellingShingle | Science::Biological sciences Wong, Brandon Han Siang Functional impact of high extracellular potassium ion on human T-cells |
| title | Functional impact of high extracellular potassium ion on human T-cells |
| title_full | Functional impact of high extracellular potassium ion on human T-cells |
| title_fullStr | Functional impact of high extracellular potassium ion on human T-cells |
| title_full_unstemmed | Functional impact of high extracellular potassium ion on human T-cells |
| title_short | Functional impact of high extracellular potassium ion on human T-cells |
| title_sort | functional impact of high extracellular potassium ion on human t cells |
| topic | Science::Biological sciences |
| url | https://hdl.handle.net/10356/141847 |
| work_keys_str_mv | AT wongbrandonhansiang functionalimpactofhighextracellularpotassiumiononhumantcells |