ArticleJournal of immunology (Baltimore, Md. : 1950)2018
Immune Checkpoint Blockade Restores HIV-Specific CD4 T Cell Help for NK Cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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Who cites it
39 citing papers in PubMed, 60 citations in OpenAlex.
- A peripheral immune signature of responsiveness to PD-1 blockade in patients with classical Hodgkin lymphoma.Nature medicine · 2020Trial
- Ebola virus glycoprotein stimulates IL-18-dependent natural killer cell responses.The Journal of clinical investigation · 2020Trial
- Interplay between natural killer cells and ferroptosis: novel insights in tumor immunity and therapeutic potential.Cell communication and signaling : CCS · 2026Review
- Article
- From natural defenders to therapeutic warriors: NK cells in HIV immunotherapy.Immunotherapy · 2025Review
- Afucosylated broadly neutralizing antibodies enhance clearance of HIV-1 infected cells through cell-mediated killing.Communications biology · 2024Article
- HIV Expression in Infected T Cell Clones.Viruses · 2024Review
- Antibody and Cell-Based Therapies against Virus-Induced Cancers in the Context of HIV/AIDS.Pathogens (Basel, Switzerland) · 2023Review
- The cytokine/chemokine response inHeliyon · 2023Review
- Mapping the interplay between NK cells and HIV: therapeutic implications.Journal of leukocyte biology · 2023Review
- Immune checkpoint inhibitors as potential therapy for reverting T-cell exhaustion and reverting HIV latency in people living with HIV.Frontiers in immunology · 2023Review
- Strategies for HIV-1 suppression through key genes and cell therapy.Frontiers in medicine · 2023Review
- Malignancy and viral infections in Sub-Saharan Africa: A review.Frontiers in virology (Lausanne, Switzerland) · 2023Article
- Targeting NK Cells for HIV-1 Treatment and Reservoir Clearance.Frontiers in immunology · 2022Review
- Inversed Ratio of CD39/CD73 Expression on γδ T Cells in HIV Versus Healthy Controls Correlates With Immune Activation and Disease Progression.Frontiers in immunology · 2022Article
- Burgeoning Exploration of the Role of Natural Killer Cells in Anti-PD-1/PD-L1 Therapy.Frontiers in immunology · 2022Review
- Integrated analysis of genome-wide DNA methylation and cancer-associated fibroblasts identified prognostic biomarkers and immune checkpoint blockade in lower grade gliomas.Frontiers in oncology · 2022Article
- Combination Immune Checkpoint Blockade Enhances IL-2 and CD107a Production from HIV-Specific T Cells Ex Vivo in People Living with HIV on Antiretroviral Therapy.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Negative Regulation and Protective Function of Natural Killer Cells in HIV Infection: Two Sides of a Coin.Frontiers in immunology · 2022Review
- Treatment of Relapsing HPV Diseases by Restored Function of Natural Killer Cells.The New England journal of medicine · 2021Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Immune exhaustion is an important feature of chronic infections, such as HIV, and a barrier to effective immunity against cancer. This dysfunction is in part controlled by inhibitory immune checkpoints. Blockade of the PD-1 or IL-10 pathways can reinvigorate HIV-specific CD4 T cell function in vitro, as measured by cytokine secretion and proliferative responses upon Ag stimulation. However, whether this restoration of HIV-specific CD4 T cells can improve help to other cell subsets impaired in HIV infection remains to be determined. In this study, we examine a cohort of chronically infected subjects prior to initiation of antiretroviral therapy (ART) and individuals with suppressed viral load on ART. We show that IFN-γ induction in NK cells upon PBMC stimulation by HIV Ag varies inversely with viremia and depends on HIV-specific CD4 T cell help. We demonstrate in both untreated and ART-suppressed individuals that dual PD-1 and IL-10 blockade enhances cytokine secretion of NK cells via restored HIV-specific CD4 T cell function, that soluble factors contribute to these immunotherapeutic effects, and that they depend on IL-2 and IL-12 signaling. Importantly, we show that inhibition of the PD-1 and IL-10 pathways also increases NK degranulation and killing of target cells. This study demonstrates a previously underappreciated relationship between CD4 T cell impairment and NK cell exhaustion in HIV infection, provides a proof of principle that reversal of adaptive immunity exhaustion can improve the innate immune response, and suggests that immune checkpoint modulation that improves CD4/NK cell cooperation can be used as adjuvant therapy in HIV infection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.