Changes in gastrointestinal microbial communities influence HIV-specific CD8+ T-cell responsiveness to immune checkpoint blockade
OBJECTIVES: The aim of this study was to examine the relationship between gut microbial communities in HIV-infected individuals on suppressive antiretroviral therapy (cART), and the peripheral HIV-Gag-specific CD8 T-cell responses before and after ex-vivo immune checkpoint blockade (ICB).
DESIGN: Thirty-four HIV-seropositive, 10 HIV-seronegative and 12 HIV-seropositive receiving faecal microbiota transplant (FMT) participants were included. Gut microbial communities, peripheral and gut associated negative checkpoint receptors (NCRs) and peripheral effector functions were assessed.
METHODS: Bacterial 16s rRNA sequencing for gut microbiome study and flow-based assays for peripheral and gut NCR and their cognate ligand expression, including peripheral HIV-Gag-specific CD8 T-cell responses before and after ex-vivo anti-PD-L1 and anti-TIGIT ICB were performed.
RESULTS: Fusobacteria abundance was significantly higher in HIV-infected donors compared to uninfected controls. In HIV-infected participants receiving Fusobacteria-free FMT, Fusobacteria persisted up to 24 weeks in stool post FMT. PD-1 TIGIT and their ligands were expanded in mucosal vs. peripheral T cells and dendritic cells, respectively. PD-L1 and TIGIT blockade significantly increased the magnitude of peripheral anti-HIV-Gag-specific CD8 T-cell responses. Higher gut Fusobacteria abundance was associated with lower magnitude of peripheral IFN-γ+ HIV-Gag-specific CD8 T-cell responses following ICB.
CONCLUSION: The gut colonization of Fusobacteria in HIV infection is persistent and may influence anti-HIV T-cell immunity to PD-1 or TIGIT blockade. Strategies modulating Fusobacteria colonization may elicit a favourable mucosal immune landscape to enhance the efficacy of ICB for HIV cure.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:34 |
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| Enthalten in: |
AIDS (London, England) - 34(2020), 10 vom: 01. Aug., Seite 1451-1460 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
SahBandar, Ivo N [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-HIV Agents |
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| Anmerkungen: |
Date Completed 18.02.2021 Date Revised 29.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1097/QAD.0000000000002557 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM312519516 |
|---|
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| 100 | 1 | |a SahBandar, Ivo N |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Changes in gastrointestinal microbial communities influence HIV-specific CD8+ T-cell responsiveness to immune checkpoint blockade |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 18.02.2021 | ||
| 500 | |a Date Revised 29.03.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVES: The aim of this study was to examine the relationship between gut microbial communities in HIV-infected individuals on suppressive antiretroviral therapy (cART), and the peripheral HIV-Gag-specific CD8 T-cell responses before and after ex-vivo immune checkpoint blockade (ICB) | ||
| 520 | |a DESIGN: Thirty-four HIV-seropositive, 10 HIV-seronegative and 12 HIV-seropositive receiving faecal microbiota transplant (FMT) participants were included. Gut microbial communities, peripheral and gut associated negative checkpoint receptors (NCRs) and peripheral effector functions were assessed | ||
| 520 | |a METHODS: Bacterial 16s rRNA sequencing for gut microbiome study and flow-based assays for peripheral and gut NCR and their cognate ligand expression, including peripheral HIV-Gag-specific CD8 T-cell responses before and after ex-vivo anti-PD-L1 and anti-TIGIT ICB were performed | ||
| 520 | |a RESULTS: Fusobacteria abundance was significantly higher in HIV-infected donors compared to uninfected controls. In HIV-infected participants receiving Fusobacteria-free FMT, Fusobacteria persisted up to 24 weeks in stool post FMT. PD-1 TIGIT and their ligands were expanded in mucosal vs. peripheral T cells and dendritic cells, respectively. PD-L1 and TIGIT blockade significantly increased the magnitude of peripheral anti-HIV-Gag-specific CD8 T-cell responses. Higher gut Fusobacteria abundance was associated with lower magnitude of peripheral IFN-γ+ HIV-Gag-specific CD8 T-cell responses following ICB | ||
| 520 | |a CONCLUSION: The gut colonization of Fusobacteria in HIV infection is persistent and may influence anti-HIV T-cell immunity to PD-1 or TIGIT blockade. Strategies modulating Fusobacteria colonization may elicit a favourable mucosal immune landscape to enhance the efficacy of ICB for HIV cure | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 650 | 7 | |a Immune Checkpoint Inhibitors |2 NLM | |
| 650 | 7 | |a RNA, Ribosomal, 16S |2 NLM | |
| 700 | 1 | |a Chew, Glen M |e verfasserin |4 aut | |
| 700 | 1 | |a Corley, Michael J |e verfasserin |4 aut | |
| 700 | 1 | |a Pang, Alina P S |e verfasserin |4 aut | |
| 700 | 1 | |a Tsai, Naoky |e verfasserin |4 aut | |
| 700 | 1 | |a Hanks, Nancy |e verfasserin |4 aut | |
| 700 | 1 | |a Khadka, Vedbar S |e verfasserin |4 aut | |
| 700 | 1 | |a Klatt, Nichole R |e verfasserin |4 aut | |
| 700 | 1 | |a Hensley-McBain, Tiffany |e verfasserin |4 aut | |
| 700 | 1 | |a Somsouk, Ma |e verfasserin |4 aut | |
| 700 | 1 | |a Vujkovic-Cvijin, Ivan |e verfasserin |4 aut | |
| 700 | 1 | |a Chow, Dominic C |e verfasserin |4 aut | |
| 700 | 1 | |a Shikuma, Cecilia M |e verfasserin |4 aut | |
| 700 | 1 | |a Ndhlovu, Lishomwa C |e verfasserin |4 aut | |
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