Anti-PD-1/PD-L1 therapy for infectious diseases: learning from the cancer paradigm

Rao, Martin; Valentini, Davide; Dodoo, Ernest; Zumla, Alimuddin; Maeurer, Markus

doi:10.1016/j.ijid.2017.01.028

Cited by 114 publications

(106 citation statements)

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“…The ability to respond with IL‐2 and IFN‐ γ may also reflect the antigen dose available to T cells in their immediate microenvironment for optimal TCR stimulation . Also, PD‐1 inhibition may be a viable therapeutic strategy to treat chronic infectious diseases, as was recently reviewed by Rao et al …”

Section: Cmv‐specific Memory Inflation Shapes Global and Anti‐tumour mentioning

confidence: 99%

The impact of inflationary cytomegalovirus‐specific memory T cells on anti‐tumour immune responses in patients with cancer

et al. 2018

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Human cytomegalovirus (CMV) is a ubiquitous, persistent beta herpesvirus. CMV infection contributes to the accumulation of functional antigen-specific CD8 T-cell pools with an effector-memory phenotype and enrichment of these immune cells in peripheral organs. We review here this 'memory T-cell inflation' phenomenon and associated factors including age and sex. 'Collateral damage' due to CMV-directed immune reactivity may occur in later stages of life - arising from CMV-specific immune responses that were beneficial in earlier life. CMV may be considered an age-dependent immunomodulator and a double-edged sword in editing anti-tumour immune responses. Emerging evidence suggests that CMV is highly prevalent in patients with a variety of cancers, particularly glioblastoma. A better understanding of CMV-associated immune responses and its implications for immune senescence, especially in patients with cancer, may aid in the design of more clinically relevant and tailored, personalized treatment regimens. 'Memory T-cell inflation' could be applied in vaccine development strategies to enrich for immune reactivity where long-term immunological memory is needed, e.g. in long-term immune memory formation directed against transformed cells.

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Section: Cmv‐specific Memory Inflation Shapes Global and Anti‐tumour mentioning

confidence: 99%

The impact of inflationary cytomegalovirus‐specific memory T cells on anti‐tumour immune responses in patients with cancer

et al. 2018

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“…[46] However, PD-1 and its ligands are usually upregulated on the surface of antigen-specific T-cells exposed to the chronicity of cancer and persistent infections, leading to cellular exhaustion and abrogation of effector functions. [47] Indeed, blocking of PD-1 pathway has resulted in successful enhancement of T-cell immunity against viral pathogens and tumors. [48] A better understanding of PD-1-related molecule expression may provide further insight into sepsis-induced immunosuppression, especially “T-cell exhaustion”.…”

Section: Programmed Cell Death-1/programmed Death-ligand 1 Pathway Prmentioning

confidence: 99%

“…[75] Antibody therapy-associated adverse events, such as diarrhea, pneumonitis, type 1 diabetes, and others, have been reported in clinical trials in cancer. [47] However, these clinical observations of anti-PD-1/PD-L1 therapy have proven that efficacy of such immune agents against tumors compensated for acceptable and manageable side effects observed in a small fraction of patients. [47] Furthermore, patients with sepsis typically may not require as prolonged therapies with anti-PD-1/PD-L1 treatment as patients with cancer.…”

Section: Limitations Of Anti-programmed Cell Death-1/programmed Deathmentioning

confidence: 99%

“…[47] However, these clinical observations of anti-PD-1/PD-L1 therapy have proven that efficacy of such immune agents against tumors compensated for acceptable and manageable side effects observed in a small fraction of patients. [47] Furthermore, patients with sepsis typically may not require as prolonged therapies with anti-PD-1/PD-L1 treatment as patients with cancer. Therefore, severe autoimmune reactions will likely be less of a problem in patients with sepsis.…”

Section: Limitations Of Anti-programmed Cell Death-1/programmed Deathmentioning

confidence: 99%

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Programmed Cell Death-1/Programmed Death-ligand 1 Pathway

Liu

2017

Chinese Medical Journal

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Objective:Sepsis remains a leading cause of death in many Intensive Care Units worldwide. Immunosuppression has been a primary focus of sepsis research as a key pathophysiological mechanism. Given the important role of the negative costimulatory molecules programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in the occurrence of immunosuppression during sepsis, we reviewed literatures related to the PD-1/PD-L1 pathway to examine its potential as a new target for sepsis treatment.Data Sources:Studies of the association between PD-1/PD-L1 and sepsis published up to January 31, 2017, were obtained by searching the PubMed database.Study Selection:English language studies, including those based on animal models, clinical research, and reviews, with data related to PD-1/PD-L1 and sepsis, were evaluated.Results:Immunomodulatory therapeutics could reverse the deactivation of immune cells caused by sepsis and restore immune cell activation and function. Blockade of the PD-1/PD-L1 pathway could reduce the exhaustion of T-cells and enhance the proliferation and activation of T-cells.Conclusions:The anti-PD-1/PD-L1 pathway shows promise as a new target for sepsis treatment. This review provides a basis for clinical trials and future studies aimed at revaluating the efficacy and safety of this targeted approach.

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“…Checkpoint inhibitors have been studied as treatment for chronic infectious diseases by restoring T-cell depletion ( 2 , 3 , 7 ), including PML, in which PD-1 on CD4 and CD8 cells has been reported ( 1 , 8 ). In a series of 740 patients given checkpoint inhibitors, serious infections developed in 7.4%, particularly in patients taking ipilimumab and nivolumab, steroids, or tumor necrosis factor antibodies for treatment of IRAEs, but few opportunistic infections and no PML were reported ( 9 ).…”

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confidence: 99%

Progressive Multifocal Leukoencephalopathy after Treatment with Nivolumab

Martinot¹,

Ahle²,

Petrosyan³

et al. 2018

Emerg. Infect. Dis.

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Anti-PD-1/PD-L1 therapy for infectious diseases: learning from the cancer paradigm

Abstract: Anti-PD-1/PD-L1 therapy holds promise as adjunctive therapy for chronic infectious diseases such as tuberculosis and HIV, and must therefore be tested in randomized clinical trials.

Cited by 114 publications

References 100 publications

The impact of inflationary cytomegalovirus‐specific memory T cells on anti‐tumour immune responses in patients with cancer

The impact of inflationary cytomegalovirus‐specific memory T cells on anti‐tumour immune responses in patients with cancer

Programmed Cell Death-1/Programmed Death-ligand 1 Pathway

Progressive Multifocal Leukoencephalopathy after Treatment with Nivolumab

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