Enhancement of Antiviral CD8+ T-Cell Responses and Complete Remission of Metastatic Melanoma in an HIV-1-Infected Subject Treated with Pembrolizumab.
Détails
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_F7B5C0ED21BA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Enhancement of Antiviral CD8+ T-Cell Responses and Complete Remission of Metastatic Melanoma in an HIV-1-Infected Subject Treated with Pembrolizumab.
Périodique
Journal of clinical medicine
ISSN
2077-0383 (Print)
ISSN-L
2077-0383
Statut éditorial
Publié
Date de publication
01/12/2019
Peer-reviewed
Oui
Volume
8
Numéro
12
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
Pembrolizumab is an immune checkpoint inhibitor against programmed cell death protein-1 (PD-1) approved for therapy in metastatic melanoma. PD-1 expression is associated with a diminished functionality in HIV-1 specific-CD8 <sup>+</sup> T cells. It is thought that PD-1 blockade could contribute to reinvigorate antiviral immunity and reduce the HIV-1 reservoir.
Upon metastatic melanoma diagnosis, an HIV-1-infected individual on stable suppressive antiretroviral regimen was treated with pembrolizumab. A PET-CT was performed before and one year after pembrolizumab initiation. We monitored changes in the immunophenotype and HIV-1 specific-CD8 <sup>+</sup> T-cell responses during 36 weeks of treatment. Furthermore, we assessed changes in the viral reservoir by total HIV-1 DNA, cell-associated HIV-1 RNA, and ultrasensitive plasma viral load.
Complete metabolic response was achieved after pembrolizumab treatment of metastatic melanoma. Activated CD8 <sup>+</sup> T-cells expressing HLA-DR <sup>+</sup> /CD38 <sup>+</sup> transiently increased over the first nine weeks of treatment. Concomitantly, there was an augmented response of HIV-1 specific-CD8 <sup>+</sup> T cells with TNF production and poly-functionality, transitioning from TNF to an IL-2 profile. Furthermore, a transient reduction of 24% and 32% in total HIV-1 DNA was observed at weeks 3 and 27, respectively, without changes in other markers of viral persistence.
These data demonstrate that pembrolizumab may enhance the HIV-1 specific-CD8 <sup>+</sup> T-cell response, marginally affecting the HIV-1 reservoir. A transient increase of CD8 <sup>+</sup> T-cell activation, TNF production, and poly-functionality resulted from PD-1 blockade. However, the lack of sustained changes in the viral reservoir suggests that viral reactivation is needed concomitantly with HIV-1-specific immune enhancement.
Upon metastatic melanoma diagnosis, an HIV-1-infected individual on stable suppressive antiretroviral regimen was treated with pembrolizumab. A PET-CT was performed before and one year after pembrolizumab initiation. We monitored changes in the immunophenotype and HIV-1 specific-CD8 <sup>+</sup> T-cell responses during 36 weeks of treatment. Furthermore, we assessed changes in the viral reservoir by total HIV-1 DNA, cell-associated HIV-1 RNA, and ultrasensitive plasma viral load.
Complete metabolic response was achieved after pembrolizumab treatment of metastatic melanoma. Activated CD8 <sup>+</sup> T-cells expressing HLA-DR <sup>+</sup> /CD38 <sup>+</sup> transiently increased over the first nine weeks of treatment. Concomitantly, there was an augmented response of HIV-1 specific-CD8 <sup>+</sup> T cells with TNF production and poly-functionality, transitioning from TNF to an IL-2 profile. Furthermore, a transient reduction of 24% and 32% in total HIV-1 DNA was observed at weeks 3 and 27, respectively, without changes in other markers of viral persistence.
These data demonstrate that pembrolizumab may enhance the HIV-1 specific-CD8 <sup>+</sup> T-cell response, marginally affecting the HIV-1 reservoir. A transient increase of CD8 <sup>+</sup> T-cell activation, TNF production, and poly-functionality resulted from PD-1 blockade. However, the lack of sustained changes in the viral reservoir suggests that viral reactivation is needed concomitantly with HIV-1-specific immune enhancement.
Mots-clé
HIV-1 curative strategies, HIV-1 reservoir, HIV-specific CD8+ T cells, Immune checkpoint inhibitors, pembrolizumab
Pubmed
Open Access
Oui
Création de la notice
15/12/2019 18:43
Dernière modification de la notice
30/04/2021 7:16