Immune Checkpoints in Viral Infections

Cai, Huiming; Liu, Ge; Zhong, Jianfeng; Zheng, Kai; Xiao, Haitao; Li, Chenyang; Song, Xun; Li, Ying; Xu, Chenshu; Wu, Haiqiang; He, Zhendan; Zhu, Qing

doi:10.3390/v12091051

Cited by 38 publications

(49 citation statements)

References 191 publications

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“…Although a positive correlation was only found between IDO1 immune checkpoint and viral load in the thymus from low virulent 3249-infected piglets, the expression of most of the immune checkpoints was up-regulated from 6 dpi onwards when a high viral load was detected, with a higher fold-change in Lena- than in 3249-infected animals. Interestingly, increased frequencies of immune checkpoints have been associated with disease progression ( 9 , 36 , 42 ), also evident in our study through the correlations between various immune checkpoints and the clinical score, temperature and microscopic lesion score in the thymus from piglets infected with the virulent Lena strain ( Figure 6 ). Therefore, the injured-thymus could induce the up-regulation of immune checkpoints in Lena-infected pigs as an attempt to control the underlying inflammatory response.…”

Section: Discussionsupporting

confidence: 75%

“…CTLA-4 binds with a higher avidity to the same ligands as CD28, namely costimulatory molecules CD80/CD86, interfering in T-cell development, proliferation and survival and suppressing negative selection at the thymus ( 35 , 38 , 40 ). CTLA-4 is also expressed in Tregs which may dampen the onset of an efficient host immune response by affecting the function and cytokine expression by T-cells, and hence, resulting in T-cell anergy ( 9 , 41 ). Immunohistochemical expression of CTLA-4 was observed within the cytoplasm of thymocytes from the corticomedullary boundary and medulla, mainly in the thymus from virulent Lena-infected piglets.…”

Section: Discussionmentioning

confidence: 99%

“…Immune checkpoint molecules are regulatory receptors expressed on immune cells, which are able to maintain selftolerance and modulate the breadth of the effector immune responses in peripheral tissues (9,10). However, during a high number of infectious diseases, up-regulation of these molecules can also limit the severe inflammatory response elicited by the infection (9,10). Sustained signaling through immune checkpoints causes T-cell dysfunction, driving effector immune cells, especially T-cells, into a state of 'exhaustion' (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

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Up-Regulation of Immune Checkpoints in the Thymus of PRRSV-1-Infected Piglets in a Virulence-Dependent Fashion

et al. 2021

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Virulent porcine reproductive and respiratory syndrome virus (PRRSV) strains, such as the Lena strain, have demonstrated a higher thymus tropism than low virulent strains. Virulent PRRSV strains lead to severe thymus atrophy, which could be related to marked immune dysregulation. Impairment of T-cell functions through immune checkpoints has been postulated as a strategy executed by PRRSV to subvert the immune response, however, its role in the thymus, a primary lymphoid organ, has not been studied yet. Therefore, the goal of this study was to evaluate the expression of selected immune checkpoints (PD1/PDL1, CTLA4, TIM3, LAG3, CD200R1 and IDO1) in the thymus of piglets infected with two different PRRSV-1 strains. Thymus samples from piglets infected with the low virulent 3249 strain, the virulent Lena strain and mock-infected were collected at 1, 3, 6, 8 and 13 days post-infection (dpi) to analyze PRRSV viral load, relative quantification and immunohistochemical staining of immune checkpoints. PD1/PDL1, CTLA4, TIM3, LAG3 and IDO1 immune checkpoints were significantly up-regulated in the thymus of PRRSV infected piglets, especially in those infected with the virulent Lena strain from 6 dpi onwards. This up-regulation was associated with disease progression, high viral load and cell death. Co-expression of these molecules can affect T-cell development, maturation and selection, negatively regulating the host immune response against PRRSV.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Up-Regulation of Immune Checkpoints in the Thymus of PRRSV-1-Infected Piglets in a Virulence-Dependent Fashion

et al. 2021

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“…The immune checkpoints are upregulated to facilitate the escape of the virus from the immune surveillance, especially, in chronic viral infections (HIV, HBV, or HCV), which lead to a persistent infection. Therefore, targeting one or more types of checkpoint receptors can result in viral elimination in preclinical studies, and ongoing clinical investigations [ 9 ].…”

Section: Immune Checkpoint Inhibitionmentioning

confidence: 99%

Immune checkpoint inhibition in COVID-19: risks and benefits

Pezeshki

Rezaei

2021

Expert Opinion on Biological Therapy

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Introduction Immune checkpoint inhibition (ICI) is a novel cancer immunotherapy, which is administered in patients with metastatic, refractory, or relapsed solid cancer types. Since the initiation of the Coronavirus Disease 2019 (COVID-19) pandemic, many studies have reported a higher severity and mortality rate of COVID-19 among patients with cancer in general. Areas covered The immunomodulatory effects of ICI can modify the patients’ immune system function in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There is controversy over whether the severity of COVID-19 in cancer patients who previously received ICI compared to other patients with cancer has increased. There is evidence that the upregulation of immune checkpoint molecules in T cells, lymphopenia, and inflammatory cytokine secretion are associated with the severity of COVID-19 symptoms. Expert opinion ICI can interrupt the T cell exhaustion and depletion by interrupting the inhibitory signaling of checkpoint molecules in T cells, and augments the immune system response in COVID-19 patients with lymphopenia. However, ICI may also increase the risk of cytokine release syndrome. ICI can be considered not only as a cancer immunotherapy but also as immunotherapy in COVID-19. More studies are needed to assess the safety of ICI in COVID-19 patients with or without cancer.

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“…In addition to cancer, several chronic and acute infectious diseases, such as malaria, human immunodeficiency virus (HIV) infection, and hepatitis B virus (HBV) infection, also exhibit high expression level of PD-1. Thus, ICI may contribute to viral clearance and has been evaluated in the treatment of infectious diseases [193,194]. A clinical study showed acceptable ICI efficacy in 73 patients with cancer who contracted HIV, as over 90% of the subjects had suppressed viral load and increased CD4+ T cell count [126].…”

Section: Immune Checkpoint Inhibitionmentioning

confidence: 99%

The intersection of COVID-19 and cancer: signaling pathways and treatment implications

et al. 2021

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The outbreak of the novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a serious public health concern. Patients with cancer have been disproportionately affected by this pandemic. Increasing evidence has documented that patients with malignancies are highly susceptible to severe infections and mortality from COVID-19. Recent studies have also elucidated the molecular relationship between the two diseases, which may not only help optimize cancer care during the pandemic but also expand the treatment for COVID-19. In this review, we highlight the clinical and molecular similarities between cancer and COVID-19 and summarize the four major signaling pathways at the intersection of COVID-19 and cancer, namely, cytokine, type I interferon (IFN-I), androgen receptor (AR), and immune checkpoint signaling. In addition, we discuss the advantages and disadvantages of repurposing anticancer treatment for the treatment of COVID-19.

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Immune Checkpoints in Viral Infections

Cited by 38 publications

References 191 publications

Up-Regulation of Immune Checkpoints in the Thymus of PRRSV-1-Infected Piglets in a Virulence-Dependent Fashion

Up-Regulation of Immune Checkpoints in the Thymus of PRRSV-1-Infected Piglets in a Virulence-Dependent Fashion

Immune checkpoint inhibition in COVID-19: risks and benefits

The intersection of COVID-19 and cancer: signaling pathways and treatment implications

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