Induction of co-inhibitory molecule CTLA-4 by human papillomavirus E7 protein through downregulation of histone methyltransferase JHDM1B expression

Zhou, Qiang; Chen, Luxia; Song, Yinjing; Ma, Li; Xiao, Peng; Chen, Lingjing; Zhen, Huimin; Han, Rui; Chen, Xianzhen; Sun, Siyuan; Tuan, Wang; Zhang, Boya; Wang, Qingqing; Cheng, Hao

doi:10.1016/j.virol.2019.10.001

Cited by 9 publications

(7 citation statements)

References 25 publications

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“…HPV, in particular, has been shown to impair host NK and T-cell antiviral responses through a variety of mechanisms including Treg recruitment, inhibition of DC maturation and suppression of NK cell cytotoxicity. In keeping with this theme, the HPV protein HPVE7, has been reported to induce CTLA-4 expression in human cervical epithelium and keratinocytes by promoting H3K36me2 at the CTLA-4 promoter (108). While no functional characterization of CTLA-4 in this context has been carried out, the authors hypothesize that it may contribute to the immunosuppressive phenotype and subsequent immune escape engendered by HPV.…”

Section: Non-hematopoietic/non-cancermentioning

confidence: 93%

Beyond T-Cells: Functional Characterization of CTLA-4 Expression in Immune and Non-Immune Cell Types

et al. 2020

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The immune response consists of a finely-tuned program, the activation of which must be coupled with inhibitory mechanisms whenever initiated. This ensures tight control of beneficial anti-pathogen and anti-tumor responses while preserving tissue integrity, promoting tissue repair, and safeguarding against autoimmunity. A cogent example of this binary response is in the mobilization of co-stimulatory and co-inhibitory signaling in regulating the strength and type of a T-cell response. Of particular importance is the costimulatory molecule CD28 which is countered by CTLA-4. While the role of CD28 in the immune response has been thoroughly elucidated, many aspects of CTLA-4 biology remain controversial. The expression of CD28 is largely constrained to constitutive expression in T-cells and as such, teasing out its function has been somewhat simplified by a limited and specific expression profile. The expression of CTLA-4, on the other hand, while reported predominantly in T-cells, has also been described on a diverse repertoire of cells within both lymphoid and myeloid lineages as well as on the surface of tumors. Nonetheless, the function of CTLA-4 has been mostly described within the context of T-cell biology. The focus on T-cell biology may be a direct result of the high degree of amino acid sequence homology and the co-expression pattern of CD28 and CTLA-4, which initially led to the discovery of CTLA-4 as a counter receptor to CD28 (for which a T-cell-activating role had already been described). Furthermore, observations of the outsized role of CTLA-4 in Treg-mediated immune suppression and the striking phenotype of T-cell hyperproliferation and resultant disease in CTLA-4−/− mice contribute to an appropriate T-cell-centric focus in the study of CTLA-4. Complete elucidation of CTLA-4 biology, however, may require a more nuanced understanding of its role in a context other than that of T-cells. This makes particular sense in light of the remarkable, yet limited utility of anti-CTLA-4 antibodies in the treatment of cancers and of CTLA-4-Ig in autoimmune disorders like rheumatoid arthritis. By fully deducing the biology of CTLA-4-regulated immune homeostasis, bottlenecks that hinder the widespread applicability of CTLA-4-based immunotherapies can be resolved.

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Section: Non-hematopoietic/non-cancermentioning

confidence: 93%

Beyond T-Cells: Functional Characterization of CTLA-4 Expression in Immune and Non-Immune Cell Types

et al. 2020

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“…Some inhibitors exhibit antiproliferative activity, and so may be used as candidates for anticancer agents (38). Human immunodeficiency virus and HPV induce epigenetic alterations in host cells by altering the levels of H3K36 methylation within the promoter region of CTLA-4 and FOXP3, resulting in several diseases and different types of cancer (40,41). Histone demethylase inhibitors combined with checkpoint blockade may be used as a novel cancer treatment strategy (41)(42)(43).…”

Section: Kdm2a Expression and Regulationmentioning

confidence: 99%

Histone demethylase KDM2A: Biological functions and clinical values (Review)

Liu

Lin

2021

Exp Ther Med

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“…Transfection of the keratinocyte cell line HaCaT with HPV11 E7 resulted in increased CTLA-4 expression in microarray, RT-PCR, and Western blot analyses. 141 These results were also reproduced in both SiHa and HeLa cells overexpressing both HPV16 E7 and HPV18 E7. The mechanism of action for E7 control of CTLA-4 expression was determined to be through the reduction of JHDM1B, a histone demethylase that led to reduced H3K36me2 enrichment in the CTLA-4 promoter.…”

Section: Therapeutic Hpv Vaccines In Combination With Other Checkpoinmentioning

confidence: 67%

<p>Therapeutic Vaccines for HPV-Associated Malignancies</p>

Rumfield

Roller

Pellom

et al. 2020

ITT

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Human papillomavirus (HPV)-related malignancies are responsible for almost all cases of cervical cancer in women, and over 50% of all cases of head and neck carcinoma. Worldwide, HPV-positive malignancies account for 4.5% of the global cancer burden, or over 600,000 cases per year. HPV infection is a pressing public health issue, as more than 80% of all individuals have been exposed to HPV by age 50, representing an important target for vaccine development to reduce the incidence of cancer and the economic cost of HPVrelated health issues. The approval of Gardasil ® as a prophylactic vaccine for high-risk HPV 16 and 18 and low-risk HPV6 and 11 for people aged 11-26 in 2006, and of Cervarix ® in 2009, revolutionized the field and has since reduced HPV infection in young populations. Unfortunately, prophylactic vaccination does not induce immunity in those with established HPV infections or HPV-induced neoplasms, and there are currently no therapeutic HPV vaccines approved by the US Food and Drug Administration. This comprehensive review will detail the progress made in the development of therapeutic vaccines against high-risk HPV types, and potential combinations with other immunotherapeutic agents for more efficient and rational designs of combination treatments for HPV-associated malignancies.

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Induction of co-inhibitory molecule CTLA-4 by human papillomavirus E7 protein through downregulation of histone methyltransferase JHDM1B expression

Cited by 9 publications

References 25 publications

Beyond T-Cells: Functional Characterization of CTLA-4 Expression in Immune and Non-Immune Cell Types

Beyond T-Cells: Functional Characterization of CTLA-4 Expression in Immune and Non-Immune Cell Types

Histone demethylase KDM2A: Biological functions and clinical values (Review)

<p>Therapeutic Vaccines for HPV-Associated Malignancies</p>

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