Antigen-specific memory NK cell responses against HIV and influenza use the NKG2/HLA-E axis

Jost, Stephanie; Lucar, Olivier; Lee, Esther; Yoder, Taylor; Kroll, Kyle; Sugawara, Sho; Smith, Scott; Jones, Rhianna; Tweet, George; Werner, Alexandra; Tomezsko, Phillip J.; Dugan, Haley L.; Ghofrani, Joshua; Rascle, Philippe; Altfeld, Marcus; Müller-Trutwin, Michaela; Goepfert, Paul; Reeves, R. Keith

doi:10.1126/sciimmunol.adi3974

Cited by 21 publications

(2 citation statements)

References 56 publications

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“…However, in patients with advanced cancer, the function of NK cells is often impaired [30]. It has been discovered that NK cells can regulate long-term immune responses and produce memory in the chemical hapten-induced contact hypersensitivity (CHS), human immunodeficiency virus-1 (HIV-1), influenza viruses, mouse cytomegalovirus (MCMV), and vesicular stomatitis virus (VSV) models [31][32][33][34][35]. However, the role of NK cells in long-term anti-tumor immunity has not been reported in tumor models.…”

Section: Discussionmentioning

confidence: 99%

Natural Killer Cells Reprogram Myeloid-Derived Suppressor Cells to Induce TNF-α Release via NKG2D–Ligand Interaction after Cryo-Thermal Therapy

You,

Wang,

Zhu

et al. 2024

IJMS

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In our previous studies, a novel cryothermal therapy (CTT) was developed to induce systemic long-term anti-tumor immunity. Natural killer (NK) cells were found to play an important role in CTT-induced long-term immune-mediated tumor control at the late stage after CTT, but the underlying mechanism is unclear. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that have potent immunosuppressive effects on T cells and weaken the long-term benefits of immunotherapy. Consequently, overcoming MDSC immunosuppression is essential for maintaining the long-term efficacy of immunotherapy. In this study, we revealed that NK cells considerably diminish MDSC accumulation at the late stage after CTT, boost T cell production, increase T cell activation, and promote MDSC maturation, culminating in Th1-dominant CD4+ T cell differentiation and enhancing NK and CD8+ T cell cytotoxicity. Additionally, NK cells activate ERK signaling in MDSCs through NKG2D-ligand interaction to increase the activity of tumor necrosis factor (TNF)-α converting enzyme (TACE)-cleaved membrane TNF-α. Furthermore, Increased TACE activity releases more soluble TNF-α from MDSCs to promote MDSC maturation. In our studies, we propose a novel mechanism by which NK cells can overcome MDSC-induced immunosuppression and maintain CTT-induced persistent anti-tumor immunity, providing a prospective therapeutic option to improve the performance of cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Natural Killer Cells Reprogram Myeloid-Derived Suppressor Cells to Induce TNF-α Release via NKG2D–Ligand Interaction after Cryo-Thermal Therapy

You,

Wang,

Zhu

et al. 2024

IJMS

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“…Jost et. al recently demonstrated increased KLRG1 expression in HIV-specific NK cell subsets among HIV-infected individuals indicating that KLRG1 can be considered a useful biomarker of HIV/SIV-specific memory NK cells 48 .…”

Section: Discussionmentioning

confidence: 99%

Novel Oral Adjuvant to Enhance Cytotoxic Memory-Like NK Cell Responses in an HIV Vaccine Platform

Alles,

Gunasena,

Isckarus

et al. 2024

Preprint

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Antibody-dependent cell-mediated cytotoxicity, mediated by natural killer (NK) cells and antibodies, emerged as a secondary correlate of protection in the RV144 HIV vaccine clinical trial, the only vaccine thus far demonstrating some efficacy in human. Therefore, leveraging NK cells with enhanced cytotoxic effector responses may bolster vaccine induced protection against HIV. Here, we investigated the effect of orally administering indole-3-carbinol (I3C), an aryl hydrocarbon receptor (AHR) agonist, as an adjuvant to an RV144-like vaccine platform in a mouse model. We demonstrate the expansion of KLRG1-expressing NK cells induced by the vaccine together with I3C. This NK cell subset exhibited enhanced vaccine antigen-specific cytotoxic memory-like features. Our study underscores the potential of incorporating I3C as an oral adjuvant to HIV vaccine platforms to enhance antigen-specific (memory-like) cytotoxicity of NK cells against HIV-infected cells. This approach may contribute to enhancing the protective efficacy of HIV preventive vaccines against HIV acquisition.

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Feeder cell training shapes the phenotype and function of in vitro expanded natural killer cells

Gao,

Mora,

Constantinides

et al. 2024

MedComm

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Natural killer (NK) cells are candidates for adoptive cell therapy, and the protocols for their activation and expansion profoundly influence their function and fate. The complexity of NK cell origin and feeder cell cues impacts the heterogeneity of expanded NK (eNK) cells. To explore this, we compared the phenotype and function of peripheral blood‐derived NK (PB‐NK) and umbilical cord blood‐derived NK (UCB‐NK) cells activated by common feeder cell lines, including K562, PLH, and 221.AEH. After first encounter, most PB‐NK cells showed degranulation independently of cytokines production. Meanwhile, most UCB‐NK cells did both. We observed that each feeder cell line uniquely influenced the activation, expansion, and ultimate fate of PB eNK and UCB eNK cells, determining whether they became cytokine producers or killer cells. In addition, they also affected the functional performance of NK cell subsets after expansion, that is, expanded conventional NK (ecNK) and expanded FcRγ– NK (eg‐NK) cells. Hence, the regulation of eNK cell function largely depends on the NK cell source and the chosen expansion system. These results underscore the significance of selecting feeder cells for NK cell expansion from various sources, notably for customized adoptive cell therapies to yield cytokine‐producing or cytotoxic eNK cells.

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Antigen-specific memory NK cell responses against HIV and influenza use the NKG2/HLA-E axis

Cited by 21 publications

References 56 publications

Natural Killer Cells Reprogram Myeloid-Derived Suppressor Cells to Induce TNF-α Release via NKG2D–Ligand Interaction after Cryo-Thermal Therapy

Natural Killer Cells Reprogram Myeloid-Derived Suppressor Cells to Induce TNF-α Release via NKG2D–Ligand Interaction after Cryo-Thermal Therapy

Novel Oral Adjuvant to Enhance Cytotoxic Memory-Like NK Cell Responses in an HIV Vaccine Platform

Feeder cell training shapes the phenotype and function of in vitro expanded natural killer cells

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