The microbial metabolite butyrate enhances the effector and memory functions of murine CD8+ T cells and improves anti-tumor activity
IntroductionCD8+ T cells are vital in the immune control of cancer and a key player in cell-based cancer immunotherapy. Recent studies have shown that microbial short-chain fatty acids (SCFA) can promote both effector and memory phenotypes in CD8+ T cells and may thereby enhance protection against c...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2025.1577906/full |
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| author | Douglas A. Gaskarth Shujun Fan Andrew J. Highton Roslyn A. Kemp |
| author_facet | Douglas A. Gaskarth Shujun Fan Andrew J. Highton Roslyn A. Kemp |
| author_sort | Douglas A. Gaskarth |
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| description | IntroductionCD8+ T cells are vital in the immune control of cancer and a key player in cell-based cancer immunotherapy. Recent studies have shown that microbial short-chain fatty acids (SCFA) can promote both effector and memory phenotypes in CD8+ T cells and may thereby enhance protection against cancer.MethodsIn this study, we determined the effect of SCFA butyrate on mouse CD8+ T cell function in vitro and in vivo, using the OT-I model.ResultsButyrate co-culture with anti-CD3 + anti-CD28 activated T cells in vitro enhanced the frequency of effector CD8+ IFN-γ-producing cells, and the amount of cytokine produced per cell. Culture with butyrate also enhanced the activation, TCR expression, and levels of phosphorylated mTOR proteins within CD8+ T cells but reduced proliferation rate and increased apoptosis. Butyrate-treated activated cells conferred tumor protection after adoptive transfer. Butyrate-treated cells were present at higher frequencies within the tumor compared to non-butyrate treated cells, and expressed IFN-γ. When analyzed using high dimensional cytometry, the tumors of mice that received butyrate-treated cells were enriched in clusters displaying an effector memory phenotype with high expression of IL-15Rβ and T-bet.DiscussionOur findings show that butyrate promotes the effector activity of CD8+ T cells in culture, which can persist in vivo while also stimulating memory phenotypes. Consequently, butyrate treatment may have strong application in T cell-based immunotherapies to improve protective cell functions and patient outcomes. |
| format | Article |
| id | doaj-art-c184a98bbc844c8688eece5feb5ec821 |
| institution | Kabale University |
| issn | 2296-858X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj-art-c184a98bbc844c8688eece5feb5ec8212025-08-20T03:24:21ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-06-011210.3389/fmed.2025.15779061577906The microbial metabolite butyrate enhances the effector and memory functions of murine CD8+ T cells and improves anti-tumor activityDouglas A. GaskarthShujun FanAndrew J. HightonRoslyn A. KempIntroductionCD8+ T cells are vital in the immune control of cancer and a key player in cell-based cancer immunotherapy. Recent studies have shown that microbial short-chain fatty acids (SCFA) can promote both effector and memory phenotypes in CD8+ T cells and may thereby enhance protection against cancer.MethodsIn this study, we determined the effect of SCFA butyrate on mouse CD8+ T cell function in vitro and in vivo, using the OT-I model.ResultsButyrate co-culture with anti-CD3 + anti-CD28 activated T cells in vitro enhanced the frequency of effector CD8+ IFN-γ-producing cells, and the amount of cytokine produced per cell. Culture with butyrate also enhanced the activation, TCR expression, and levels of phosphorylated mTOR proteins within CD8+ T cells but reduced proliferation rate and increased apoptosis. Butyrate-treated activated cells conferred tumor protection after adoptive transfer. Butyrate-treated cells were present at higher frequencies within the tumor compared to non-butyrate treated cells, and expressed IFN-γ. When analyzed using high dimensional cytometry, the tumors of mice that received butyrate-treated cells were enriched in clusters displaying an effector memory phenotype with high expression of IL-15Rβ and T-bet.DiscussionOur findings show that butyrate promotes the effector activity of CD8+ T cells in culture, which can persist in vivo while also stimulating memory phenotypes. Consequently, butyrate treatment may have strong application in T cell-based immunotherapies to improve protective cell functions and patient outcomes.https://www.frontiersin.org/articles/10.3389/fmed.2025.1577906/fullbutyratecancerCD8+ T cellsactivationeffector functionshort-chain fatty acids |
| spellingShingle | Douglas A. Gaskarth Shujun Fan Andrew J. Highton Roslyn A. Kemp The microbial metabolite butyrate enhances the effector and memory functions of murine CD8+ T cells and improves anti-tumor activity Frontiers in Medicine butyrate cancer CD8+ T cells activation effector function short-chain fatty acids |
| title | The microbial metabolite butyrate enhances the effector and memory functions of murine CD8+ T cells and improves anti-tumor activity |
| title_full | The microbial metabolite butyrate enhances the effector and memory functions of murine CD8+ T cells and improves anti-tumor activity |
| title_fullStr | The microbial metabolite butyrate enhances the effector and memory functions of murine CD8+ T cells and improves anti-tumor activity |
| title_full_unstemmed | The microbial metabolite butyrate enhances the effector and memory functions of murine CD8+ T cells and improves anti-tumor activity |
| title_short | The microbial metabolite butyrate enhances the effector and memory functions of murine CD8+ T cells and improves anti-tumor activity |
| title_sort | microbial metabolite butyrate enhances the effector and memory functions of murine cd8 t cells and improves anti tumor activity |
| topic | butyrate cancer CD8+ T cells activation effector function short-chain fatty acids |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2025.1577906/full |
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