Prostaglandin E2 and PD-1 mediated inhibition of antitumor CTL responses in the human tumor microenvironment

Miao, Jie; Lu, Xu; Hu, Yuefeng; Piao, Chunmei; Wu, Xuan; Liu, Xuesong; Huang, Caiting; Wang, Yue; Li, Dan; Liu, Jingwei

doi:10.18632/oncotarget.21155

Cited by 55 publications

(38 citation statements)

References 38 publications

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“…Recently, several studies have demonstrated an association between PGE 2 elevation and upregulated expression of other immunoinhibitory molecules, such as PD-1, in human cancer (53,54). In addition, dual blockade of PGE 2 and PD-1 improved tumor eradication in a mouse model (55).…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E2–Induced Immune Exhaustion and Enhancement of Antiviral Effects by Anti–PD-L1 Antibody Combined with COX-2 Inhibitor in Bovine Leukemia Virus Infection

Sajiki

Konnai

Okagawa

et al. 2019

The Journal of Immunology

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Bovine leukemia virus (BLV) infection is a chronic viral infection of cattle and endemic in many countries, including Japan. Our previous study demonstrated that PGE 2 , a product of cyclooxygenase (COX) 2, suppresses Th1 responses in cattle and contributes to the progression of Johne disease, a chronic bacterial infection in cattle. However, little information is available on the association of PGE 2 with chronic viral infection. Thus, we analyzed the changes in plasma PGE 2 concentration during BLV infection and its effects on proviral load, viral gene transcription, Th1 responses, and disease progression. Both COX2 expression by PBMCs and plasma PGE 2 concentration were higher in the infected cattle compared with uninfected cattle, and plasma PGE 2 concentration was positively correlated with the proviral load. BLV Ag exposure also directly enhanced PGE 2 production by PBMCs. Transcription of BLV genes was activated via PGE 2 receptors EP2 and EP4, further suggesting that PGE 2 contributes to disease progression. In contrast, inhibition of PGE 2 production using a COX-2 inhibitor activated BLV-specific Th1 responses in vitro, as evidenced by enhanced T cell proliferation and Th1 cytokine production, and reduced BLV proviral load in vivo. Combined treatment with the COX-2 inhibitor meloxicam and anti-programmed death-ligand 1 Ab significantly reduced the BLV proviral load, suggesting a potential as a novel control method against BLV infection. Further studies using a larger number of animals are required to support the efficacy of this treatment for clinical application.

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Section: Discussionmentioning

confidence: 99%

Prostaglandin E2–Induced Immune Exhaustion and Enhancement of Antiviral Effects by Anti–PD-L1 Antibody Combined with COX-2 Inhibitor in Bovine Leukemia Virus Infection

Sajiki

Konnai

Okagawa

et al. 2019

The Journal of Immunology

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“…The disruption of COX2–PGE 2 signaling by COX‐2 inhibitors or antagonists of PGE 2 receptors enhance the effect of PD‐1 blockade, suggesting that the COX‐2–PGE 2 axis has antagonizing effects on PD‐1 inhibitors . Interestingly, the TLR9 agonist upregulates COX‐2 expression through nuclear factor‐κB activation .…”

Section: Discussionmentioning

confidence: 99%

“…5 The disruption of COX2-PGE 2 signaling by COX-2 inhibitors or antagonists of PGE 2 receptors enhance the effect of PD-1 blockade, suggesting that the COX-2-PGE 2 axis has antagonizing effects on PD-1 inhibitors. 6 Interestingly, the TLR9 agonist upregulates COX-2 expression through nuclear factor-jB activation. 7 Therefore, when the TLR9 subfamily agonist is delivered concomitantly with PD-1 inhibitors, the agonist may counteract the anticancer property of PD-1 inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Eruptive squamous cell carcinoma in a patient treated with concomitant pembrolizumab and imiquimod

Kanekura

Arimura

Kirishima

et al. 2019

The Journal of Dermatology

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Pembrolizumab, a humanized monoclonal antibody against programmed cell death 1, is used for various malignant neoplasms. Toll‐like receptor (TLR) agonists, specifically targeting the TLR9 subfamily (TLR7–9), are treatment options for solid tumors and hematological malignancies. We experienced a case of eruptive squamous cell carcinoma (SCC) in a patient treated concomitantly with pembrolizumab and imiquimod, a TLR7 agonist. A 75‐year‐old woman who was given a diagnosis of bladder cancer with lung metastasis received pembrolizumab for 3 months when she was referred to our department for the evaluation of skin rashes on her hands. Her skin lesions were diagnosed as well‐differentiated SCC and treated with topical imiquimod. Two months after the start of imiquimod, more than 10 reddish papules appeared on her hands. The histological diagnosis of a new plaque was the same as an earlier biopsy. We herein describe this case in detail and provide a published work review.

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“…Combined blockade of COX-PGE 2 signalling and PD-1/PD-L1 augments T cell responses and improves control of viral infection and tumour growth (J. H. Chen et al, 2015;Miao et al, 2017;Sajiki et al, 2019).…”

Section: Pge 2 On T Cell Functionsmentioning

confidence: 99%

Non‐steroidal anti‐inflammatory drugs, prostaglandins, and COVID‐19

Robb

Goepp

Rossi

et al. 2020

British J Pharmacology

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the novel coronavirus disease 2019 (COVID-19), a highly pathogenic and sometimes fatal respiratory disease responsible for the current 2020 global pandemic. Presently, there remains no effective vaccine or efficient treatment strategies against COVID-19. Non-steroidal anti-inflammatory drugs (NSAIDs) are medicines very widely used to alleviate fever, pain, and inflammation (common symptoms of COVID-19 patients) through effectively blocking production of prostaglandins (PGs) via inhibition of cyclooxyganase enzymes. PGs can exert either proinflammatory or anti-inflammatory effects depending on the inflammatory scenario. In this review, we survey the potential roles that NSAIDs and PGs may play during SARS-CoV-2 infection and the development and progression of COVID-19.

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Prostaglandin E2 and PD-1 mediated inhibition of antitumor CTL responses in the human tumor microenvironment

Cited by 55 publications

References 38 publications

Prostaglandin E2–Induced Immune Exhaustion and Enhancement of Antiviral Effects by Anti–PD-L1 Antibody Combined with COX-2 Inhibitor in Bovine Leukemia Virus Infection

Prostaglandin E2–Induced Immune Exhaustion and Enhancement of Antiviral Effects by Anti–PD-L1 Antibody Combined with COX-2 Inhibitor in Bovine Leukemia Virus Infection

Eruptive squamous cell carcinoma in a patient treated with concomitant pembrolizumab and imiquimod

Non‐steroidal anti‐inflammatory drugs, prostaglandins, and COVID‐19

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