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

Chiu, Chris; Chang, Judy; Dantanarayana, Ashanti; Solomon, Ajantha; Evans, Vanessa A.; Pascoe, Rachel; Gubser, Céline; Trautman, Lydie; Fromentin, Rémi; Chomont, Nicolas; McMahon, James; Cameron, Paul; Rasmussen, Thomas A; Lewin, Sharon R

doi:10.4049/jimmunol.2100367

Cited by 20 publications

(22 citation statements)

References 75 publications

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“…[38][39][40] Blockade of PD-1 with the anti-PD-1 antibody pembrolizumab was recently shown in a clinical trial to induce expression of both cell-associated unspliced HIV RNA and plasma RNA in PWH on ART. 41 Antibodies to immune checkpoints can also increase HIV-specific T-cell function ex vivo 42 and in vivo; 43 however, whether this increase in HIVspecific T-cell function can also clear infected cells in vivo remains unknown. Given the commonly reported immune-related adverse events following anti-PD-1, that can be irreversible, there are some concerns about whether these antibodies can be safely pursued in PWH.…”

Section: Enhancing Functionmentioning

confidence: 99%

The role of latency reversal in HIV cure strategies

Tanaka

Kim

Roche

et al. 2022

J of Medical Primatology

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One strategy to eliminate latently infected cells that persist in people with HIV on antiretroviral therapy is to activate virus transcription and virus production to induce virus or immune-mediated cell death. This is called latency reversal. Despite clear activity of multiple latency reversal agents in vitro, clinical trials of latency-reversing agents have not shown significant reduction in latently infected cells. We review new insights into the biology of HIV latency and discuss novel approaches to enhance the efficacy of latency reversal agents.

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Section: Enhancing Functionmentioning

confidence: 99%

The role of latency reversal in HIV cure strategies

Tanaka

Kim

Roche

et al. 2022

J of Medical Primatology

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“…Immune checkpoint blockade in HIV has demonstrated improved HIV specific CD8 degranulation in vitro ( 83 , 84 ). Modest improvement in CD8 function has also been demonstrated in vivoin vitro ( 85 ).…”

Section: The “Kill”: Bcl-2 Inhibitors and Immune Effector Potentiationmentioning

confidence: 99%

Prime, shock and kill: BCL-2 inhibition for HIV cure

Chandrasekar

Badley²

2022

Front. Immunol.

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While modern HIV therapy can effectively suppress viral replication, the persistence of the latent reservoir posits the greatest hurdle to complete cure. The “shock and kill” strategy is under investigation for HIV therapy, aiming to reactivate latent HIV, and subsequently eliminate it through anti-retroviral therapy and host immune function. However, thus far, studies have yielded suboptimal results, stemming from a combination of ineffective latency reversal and poor immune clearance. Concomitantly, studies have now revealed the importance of the BCL-2 anti-apoptotic protein as a critical mediator of infected cell survival, reservoir maintenance and immune evasion in HIV. Furthermore, BCL-2 inhibitors are now recognized for their anti-HIV effects in pre-clinical studies. This minireview aims to examine the intersection of BCL-2 inhibition and current shock and kill efforts, hoping to inform future studies which may ultimately yield a cure for HIV.

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“…In CD8 + T cells derived from cancer patients, TIGIT is upregulated along with PD-1, and combination therapy invariably results in a significant outcome of tumor growth inhibition [ 70 , 71 ]. A recent study demonstrates that the combination blockade of LAG-3, CTLA-4, or TIGIT increases the frequency of cells expressing CD107a and IL-2, which are associated with cytotoxicity and survival of HIV-specific CD4 + and CD8 + T cells in HAART-treated PLWH [ 72 ].…”

Section: Elevated Expression Of T Cell Immune Checkpoint Molecules In...mentioning

confidence: 99%

Immune Checkpoint Molecules and Glucose Metabolism in HIV-Induced T Cell Exhaustion

et al. 2022

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The progressive decline of CD8+ cytotoxic T cells in human immunodeficiency virus (HIV)-infected patients due to infection-triggered cell exhaustion and cell death is significantly correlated with disease severity and progression into the life-threatening acquired immunodeficiency syndrome (AIDS) stage. T cell exhaustion is a condition of cell dysfunction despite antigen engagement, characterized by augmented surface expression of immune checkpoint molecules such as programmed cell death protein 1 (PD-1), which suppress T cell receptor (TCR) signaling and negatively impact the proliferative and effector activities of T cells. T cell function is tightly modulated by cellular glucose metabolism, which produces adequate energy to support a robust reaction when battling pathogen infection. The transition of the T cells from an active to an exhausted state following pathogen persistence involves a drastic change in metabolic activity. This review highlights the interplay between immune checkpoint molecules and glucose metabolism that contributes to T cell exhaustion in the context of chronic HIV infection, which could deliver an insight into the rational design of a novel therapeutic strategy.

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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

Cited by 20 publications

References 75 publications

The role of latency reversal in HIV cure strategies

The role of latency reversal in HIV cure strategies

Prime, shock and kill: BCL-2 inhibition for HIV cure

Immune Checkpoint Molecules and Glucose Metabolism in HIV-Induced T Cell Exhaustion

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