HIV reservoir dynamics in HAART-treated poor immunological responder patients under IL-7 therapy

Logerot, Sandrine; Rancez, Magali; Muylder, Bénédicte Charmeteau-De; Figueiredo-Morgado, Suzanne; Rozlan, Sandra; Tambussi, Giuseppe; Beq, Stéphanie; Couëdel-Courteille, Anne; Cheynier, Rémi

doi:10.1097/qad.0000000000001752

Cited by 11 publications

(7 citation statements)

References 36 publications

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“…Exogenous administration of IL-7 is associated with dose-dependent increases in CD4 and CD8 T cells in PLWH on ART (143), including HIV-specific CD8 T cells (83). In patients with suppressed HIV, administration of IL-7 led to transient increases in HIV viral load without observed clinical sequelae (84), as well as enhanced anti-HIV CD8 activity. Another T-cell growth factor, IL-15, induces antigen-specific T-cell proliferation, most pronounced in the CD8 compartment (94, 95, 144, 145).…”

Section: Cancer Immunotherapy and Hiv Persistancementioning

confidence: 99%

Immunotherapy in People With HIV and Cancer

2019

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HIV infection alters the natural history of several cancers, in large part due to its effect on the immune system. Immune function in people living with HIV may vary from normal to highly dysfunctional and is largely dependent on the timing of initiation (and continuation) of effective antiretroviral therapy (ART). An individual's level of immune function in turn affects their cancer risk, management, and outcomes. HIV-associated lymphocytopenia and immune dysregulation permit immune evasion of oncogenic viruses and premalignant lesions and are associated with inferior outcomes in people with established cancers. Various types of immunotherapy, including monoclonal antibodies, interferon, cytokines, immunomodulatory drugs, allogeneic hematopoietic stem cell transplant, and most importantly ART have shown efficacy in HIV-related cancer. Emerging data suggest that checkpoint inhibitors targeting the PD-1/PD-L1 pathway can be safe and effective in people with HIV and cancer. Furthermore, some cancer immunotherapies may also affect HIV persistence by influencing HIV latency and HIV-specific immunity. Studying immunotherapy in people with HIV and cancer will advance clinical care of all people living with HIV and presents a unique opportunity to gain insight into mechanisms for HIV eradication.

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Section: Cancer Immunotherapy and Hiv Persistancementioning

confidence: 99%

Immunotherapy in People With HIV and Cancer

2019

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“…IL-7 signaling plays a central role in T-cell homeostatic proliferation and memory differentiation [23,24,38,[51][52][53]. Recombinant human interleukin 7 (rh-IL-7) has been used in various clinical trials, and has shown favorable effects on immunological recovery in HIV-infected patients [54,55]. Moreover, clinical studies have indicated that rh-IL-7 therapy could enhance the survival and proliferation of both naïve and memory T cells [56][57][58][59], reconstitute T-cell populations in gutassociated lymphoid tissue [60], increase the number of circulat-ing HIV-specific CD8 + T cells [61], and promote the functional recovery of antigen specific-memory T-cell responses [62].…”

Section: Discussionmentioning

confidence: 99%

Compromised long‐lived memory CD8⁺ T cells are associated with reduced IL‐7 responsiveness in HIV‐infected immunological nonresponders

et al. 2021

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Immune deficiency is one of the hallmarks of HIV infection and a major cause of adverse outcomes in people living with HIV (PLWH). Long‐lived memory CD8+ T cells (LLMCs) are essential executors of long‐term protective immunity; however, the generation and maintenance of LLMCs during chronic HIV infection are not well understood. In the present study, we analyzed circulating LLMCs in healthy controls (HCs) and PLWH with different disease statuses, including treatment naïve patients (TNs), complete responders (CRs), and immunological nonresponders (INRs). We found that both TNs and INRs showed severely compromised LLMCs compared with HCs and CRs, respectively. The decrease of LLMCs in TNs correlated positively with the reduction of their precursors, namely memory precursor effector T cells (MPECs), which might be associated with elevated pro‐inflammatory cytokines. Strikingly, INRs showed an accumulation of MPECs, which exhibited diminished responsiveness to interleukin 7 (IL‐7), thereby indicating abrogated differentiation into LLMCs. Moreover, in vitro studies showed that treatment with dexamethasone could improve the IL7‐phosphorylated (p)‐signal transducer and activator of transcription (STAT5) response by upregulating the expression of the interleukin 7 receptor (IL‐7Rα) on MPECs in INRs. These findings provide insights that will encourage the development of novel therapeutics to improve immune function in PLWH.

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“…This may explain observations that disulfiram was inefficient to reduce the size of HIV-1 reservoir in a single-arm pilot study [ 53 ] as well as bryostatin not affecting the transcription of latent HIV-1 in a double-blind phase I pilot clinical-trial [ 54 ]. IL-7 use was even associated with transient expansion of HIV-1 reservoir in two independent studies [ 55 , 56 ]. However, it is important to highlight that modulating more genes does not necessarily translate to more efficiency in reservoir reactivation either; indeed it could lead to generalized toxicity or activation of the immune system due to activation of several “off-target” genes [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Reanalysis of Gene Expression Profiles of CD4+ T Cells Treated with HIV-1 Latency Reversal Agents

2020

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The human immunodeficiency virus (HIV-1) causes a progressive depletion of CD4+ T cells, hampering immune function. Current experimental strategies to fight the virus focus on the reactivation of latent HIV-1 in the viral reservoir to make the virus detectable by the immune system, by searching for latency reversal agents (LRAs). We hypothesize that if common molecular pathways elicited by the presence of LRAs are known, perhaps new, more efficient, “shock-and-kill” strategies can be found. Thus, the objective of the present study is to re-evaluate RNA-Seq assays to find differentially expressed genes (DEGs) during latency reversal via transcriptome analysis. We selected six studies (45 samples altogether: 16 negative controls and 29 LRA-treated CD4+ T cells) and 11 LRA strategies through a systematic search in Gene Expression Omnibus (GEO) and PubMed databases. The raw reads were trimmed, counted, and normalized. Next, we detected consistent DEGs in these independent experiments. AZD5582, romidepsin, and suberanilohydroxamic acid (SAHA) were the LRAs that modulated most genes. We detected 948 DEGs shared by those three LRAs. Gene ontology analysis and cross-referencing with other sources of the literature showed enrichment of cell activation, differentiation and signaling, especially mitogen-activated protein kinase (MAPK) and Rho-GTPases pathways.

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HIV reservoir dynamics in HAART-treated poor immunological responder patients under IL-7 therapy

Cited by 11 publications

References 36 publications

Immunotherapy in People With HIV and Cancer

Immunotherapy in People With HIV and Cancer

Compromised long‐lived memory CD8⁺ T cells are associated with reduced IL‐7 responsiveness in HIV‐infected immunological nonresponders

Reanalysis of Gene Expression Profiles of CD4+ T Cells Treated with HIV-1 Latency Reversal Agents

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HIV reservoir dynamics in HAART-treated poor immunological responder patients under IL-7 therapy

Cited by 11 publications

References 36 publications

Immunotherapy in People With HIV and Cancer

Immunotherapy in People With HIV and Cancer

Compromised long‐lived memory CD8+ T cells are associated with reduced IL‐7 responsiveness in HIV‐infected immunological nonresponders

Reanalysis of Gene Expression Profiles of CD4+ T Cells Treated with HIV-1 Latency Reversal Agents

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Compromised long‐lived memory CD8⁺ T cells are associated with reduced IL‐7 responsiveness in HIV‐infected immunological nonresponders