Human cytomegalovirus IE2 protein regulates macrophage-mediated immune escape by upregulating GRB2 expression in UL122 genetically modified mice

Yang, Yanan; Ren, Guohua; Wang, Zhifei; Wang, Bin

doi:10.5582/bst.2019.01197

Cited by 6 publications

(5 citation statements)

References 45 publications

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“…Human cytomegalovirus IE2 protein increases the expression of M2 Mø-linked cytokines IL-4 and IL-13 by up-regulating the expression of UL122, thereby promoting Mø-mediated immune escape. 31 This work found that high AIM2 expression in LUAD Mø promoted PD-L1 expression to repress immune infiltration of CD8 + T cells, thereby fostering tumor immune escape.…”

Section: Discussionmentioning

confidence: 85%

AIM2 fosters lung adenocarcinoma immune escape by modulating PD-L1 expression in tumor-associated macrophages via JAK/STAT3

Ye,

Yu,

et al. 2023

Human Vaccines & Immunotherapeutics

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This work was devised to discuss the effect of AIM2 on the immunosuppression of LUAD tumors, as well as its molecular mechanism. An allograft mouse model was built. Mouse macrophages were isolated and collected. The infiltration level of Mø and expression of M1 Mø, M2 Mø markers, and PD-L1 were assayed by IHC and flow cytometry. Expression levels of M1 Mø and M2 Mø marker genes and PD-L1 were detected by qPCR. The expression of proteins linked with JAK/STAT3 was tested by western blot. CD8 + T cells and NK cells were activated in vitro and co-cultured with mouse macrophages, and their cytotoxicity was detected by LDH method. The proportion of CD206+PD-L1+ cells and the activation and proliferation of CD8 + T cells were assayed by flow cytometry. Multicolor immunofluorescence was utilized to assay the co-localization of proteins. AIM2 demonstrated a high expression in LUAD, exhibiting a conspicuous positive correlation with the expression of the M2 Mø markers as well as PD-L1. Expression of M1 markers was upregulated after knockdown of AIM2, while M2 markers expression and PD-L1 were downregulated, and the colocalization of proteins linked with PD-L1 and M2 Mø was decreased. The infiltration and cytotoxicity of CD8 + T cells and NK cells increased after silencing AIM2. After the knockdown of AIM2, which was enriched in the JAK/STAT3 pathway, the phosphorylation levels of JAK1, JAK2, and STAT3 were reduced, the immune infiltration level of CD8 + T cells increased, and the co-localization level of PD-L1 and PD-1 dropped. The activity and proliferation level of CD8 + T cells were increased with the reduced PD-1 expression. AIM2 fosters M2 Mø polarization and PD-L1 expression via the JAK/STAT3 pathway. Moreover, AIM2 promotes the immune escape of LUAD via the PD-1/PD-L1 axis. Our work may blaze a trail for the clinical treatment of LUAD.

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Section: Discussionmentioning

confidence: 85%

AIM2 fosters lung adenocarcinoma immune escape by modulating PD-L1 expression in tumor-associated macrophages via JAK/STAT3

Ye,

Yu,

et al. 2023

Human Vaccines & Immunotherapeutics

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“…IE often serve as transcription factors that regulate the expression of both viral and host cellular genes, which are crucial for efficient viral replication. IE can also activate production of early and late structural viral proteins, including the viral tegument protein pp65 [20]. HCMV-pp65 is an immunomodulatory protein.…”

Section: Discussionmentioning

confidence: 99%

Detection of Human Cytomegalovirus in Patients with Epithelial Ovarian Cancer and its Impacts on Survival

Yin

Chen

Zhao

et al. 2020

Preprint

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Background: The cause of epithelial ovarian cancer(EOC) is not elucidated. It has been proved that infectious agents could contribute to ovarian carcinogenesis. Human cytomegalovirus (HCMV) has been detected in several types of tumors. Objective: To investigate the potential role of HCMV infection in EOC, we evaluated the prevalence of HCMV proteins in EOC tissue sections and its impacts on patients’ survival. Methods: Formalin-fixed, paraffin-embedded tissues from 66 patients with EOC and 30 patients with benign ovarian cystadenoma were studied. Specimens were detected for expression of HCMV immediate-early protein (IE) and HCMV tegument protein (pp65) by immunohistochemistry. Results: HCMV-IE protein expression was detected in 82% of EOC and 36% of benign tumors; pp65 was detected in 97% of EOC and 63% of benign tumors. Extensive expression of HCMV-IE protein was associated with higher stage of EOC. Reactivation of latent HCMV within the tumor at interval debulking surery may be induced by neoadjuvant chemotherapy before surgery. Extensive HCMV-IE expression was associated with shorter median overall survival than focal or negative expression (39 versus 41 months, P = 0.03). Conclusions: This study demonstrate a high prevalence of HCMV proteins in tissue sections from patients with EOC. HCMV infections can be potential risks for EOC development. The relationship between HCMV and clinical outcomes highlight the need for further researches on the oncomodulatory role of HCMV in ovarian cancer.

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“…HCMV-IE often serves as transcription factors that regulate the expression of both viral and host cellular genes, which are crucial to efficient viral replication. IE can also activate production of early and late structural viral proteins, including the viral tegument protein pp65 [22]. HCMV-pp65 is an immunomodulatory protein.…”

Section: Discussionmentioning

confidence: 99%

Detection of Human Cytomegalovirus in Patients with Epithelial Ovarian Cancer and its Impacts on Survival

Yin

Chen

Zhao

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: The cause of epithelial ovarian cancer(EOC) is not elucidated. Viral infection may induce chronic inflammatory infection and play a role in the pathogenesis of cancers. Some viruses are considered to be oncomodulatory, modulating cellular pathways such as cell proliferation, tumor progression, vascular disease development, and immune evasion. Human cytomegalovirus (HCMV) has been detected in several types of cancers including ovarian cancer. However, the role of HCMV in ovarian carcinogenesis remains controversial.Objective: To investigate the potential role of HCMV infection in EOC, we evaluated the prevalence of HCMV proteins in EOC tissue and its impacts on patients’ survival.Methods: Formalin-fixed paraffin-embedded tissues from 66 patients with EOC and 30 patients with benign ovarian cystadenoma were studied. Specimens were analyzed for expression of HCMV immediate early protein (IE) and HCMV tegument protein (pp65) by immunohistochemistry. Results: HCMV-IE protein expression was detected in 82% of EOC and 36% of benign tumors; pp65 was detected in 97% of EOC and 63% of benign tumors. Extensive HCMV-IE protein expression was associated with higher stage of EOC. Reactivation of latent HCMV within the tumor at interval debulking surgery may be induced by neoadjuvant chemotherapy before surgery. Extensive HCMV-IE expression was associated with shorter median overall survival than focal or negative expression (39 versus 41 months, P=0.03). Multivariate analysis indicated that HCMV-IE expression was an independent prognostic factor for overall survival (P = 0.034). Conclusions: This study demonstrate a high prevalence of HCMV proteins in tissue sections from patients with EOC. HCMV infection can be potential risk factor for EOC development. Extensive HCMV-IE expression indicated a poor prognosis. The relationship between HCMV and clinical outcomes highlight the need for further researches on the oncomodulatory role of HCMV in ovarian cancer.

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Human cytomegalovirus IE2 protein regulates macrophage-mediated immune escape by upregulating GRB2 expression in UL122 genetically modified mice

Cited by 6 publications

References 45 publications

AIM2 fosters lung adenocarcinoma immune escape by modulating PD-L1 expression in tumor-associated macrophages via JAK/STAT3

AIM2 fosters lung adenocarcinoma immune escape by modulating PD-L1 expression in tumor-associated macrophages via JAK/STAT3

Detection of Human Cytomegalovirus in Patients with Epithelial Ovarian Cancer and its Impacts on Survival

Detection of Human Cytomegalovirus in Patients with Epithelial Ovarian Cancer and its Impacts on Survival

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