Rescue of exhausted CD8 T cells by PD-1–targeted therapies is CD28-dependent

Kamphorst, Alice O.; Wieland, Andreas; Nasti, Tahseen H.; Yang, Shu; Zhang, Ruan; Barber, Daniel L.; Konieczny, Bogumila T.; Daugherty, Candace; Koenig, Lydia; Ke, Yu; Sica, Gabriel; Sharpe, Arlene H.; Freeman, Gordon J.; Blazar, Bruce R.; Turka, Laurence A.; Owonikoko, Taofeek K.; Pillai, Rathi N.; Ramalingam, Suresh S.; Araki, Koichi; Ahmed, Rafi

doi:10.1126/science.aaf0683

Science

2017

DOI: 10.1126/science.aaf0683

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Rescue of exhausted CD8 T cells by PD-1–targeted therapies is CD28-dependent

Alice O. Kamphorst

¹

,

Andreas Wieland

²

,

Tahseen H. Nasti

³

et al.

Abstract: Programmed cell death-1 (PD-1) targeted therapies enhance T cell responses and show efficacy in multiple cancers but the role of costimulatory molecules in this T cell rescue remains elusive. Here we demonstrate that the CD28/B7 costimulatory pathway is essential for effective PD-1 therapy during chronic viral infection of mice. Conditional gene deletion showed a cell-intrinsic requirement of CD28 for CD8 T cell proliferation after PD-1 blockade. B7-costimulation was also necessary for effective PD-1 therapy i… Show more

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Cited by 991 publications

(813 citation statements)

References 29 publications

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45

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757

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“…In line with this hypothesis, analysis of gp100-specific CD8 T cells of two melanoma patients showed expansion of tumor-reactive CD8 T cells upon PD-1 blockade in the tumor whereas an expansion of the T cell response was detected infrequently in peripheral blood (16). Second, contrary to previous studies suggesting a potential role of PD-1 blockade in priming of novel CD8 T cell responses (10)(11)(12)(13), our data show that PD-1 blockade does not significantly increase the breadth of the melanoma-reactive CD8 T cell response. In line with these findings, a recent study has demonstrated in a mouse model that anti-PD-1 therapy as monotherapy is insufficient for the priming of naïve tumor-specific CD8 T cells (28).…”

Section: Discussioncontrasting

confidence: 99%

Differential effects of PD-1 and CTLA-4 blockade on the melanoma-reactive CD8 T cell response

Gangaev

¹

,

Rozeman

²

,

Rohaan

³

et al. 2020

Preprint

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

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“…In line with this hypothesis, analysis of gp100-specific CD8 T cells of two melanoma patients showed expansion of tumor-reactive CD8 T cells upon PD-1 blockade in the tumor whereas an expansion of the T cell response was detected infrequently in peripheral blood (16). Second, contrary to previous studies suggesting a potential role of PD-1 blockade in priming of novel CD8 T cell responses (10)(11)(12)(13), our data show that PD-1 blockade does not significantly increase the breadth of the melanoma-reactive CD8 T cell response. In line with these findings, a recent study has demonstrated in a mouse model that anti-PD-1 therapy as monotherapy is insufficient for the priming of naïve tumor-specific CD8 T cells (28).…”

Section: Discussioncontrasting

confidence: 99%

Differential effects of PD-1 and CTLA-4 blockade on the melanoma-reactive CD8 T cell response

Gangaev

¹

,

Rozeman

²

,

Rohaan

³

et al. 2020

Preprint

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…However, the massive rollout or implementation of statin therapy in concert with ART during HIV infection is limited by drug to drug interactions [ 63 ]. Despite several study groups showing that lowering or blockade of checkpoint inhibitors like PD-1 results in the rescue of T cell function, we did not observe any differences in cytokine specific responses to Gag in A. indica treated versus untreated conditions [ 64 , 65 ].…”

Section: Discussioncontrasting

confidence: 99%

In-vitro Immunomodulatory activity of Azadirachta indica A.Juss. Ethanol: water mixture against HIV associated chronic CD4+ T-cell activation/ exhaustion

Olwenyi

¹

,

Asingura

²

,

Naluyima

³

et al. 2021

BMC Complement Med Ther

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…We found that patients that responded to PD-1 blockade experienced a greater increase in expression of the proliferation marker Ki67 particularly in CD28-expressing CD8 T cells. This is in accordance with previously published data showing an increase in CD8 T cell proliferation that correlates with clinical response and is largely driven by CD28-expressing CD8 T cells [ 13 , 27 ]. Furthermore, we show that the frequency of proliferating CD28+ CD8 T cells directly correlates with the frequency of CXCR3- and ICOS-expressing CD8 T cells at the 6-week timepoint, suggesting that the latter could be used as surrogate markers for PD-1 induced proliferation, avoiding the need for intracellular Ki67 staining.…”

Section: Discussionsupporting

confidence: 93%

Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood

Edner

¹

,

Ntavli

²

,

Petersone

³

et al. 2023

Immunotherapy Advances

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

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