Epigenetic Reprogramming of CD4+ Helper T Cells as a Strategy to Improve Anticancer Immunotherapy

Renaude, Elodie; Kroemer, Marie; Borg, Christophe; Peixoto, Paul; Hervouet, Éric; Loyon, Romain; Adotévi, Olivier

doi:10.3389/fimmu.2021.669992

Cited by 21 publications

(20 citation statements)

References 125 publications

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“…Here, we observed that HSF2 was significantly and negatively associated with the abundance of infiltrating macrophages, including M1 and M2 phenotypes, in most tumors, and illustrating the complexity of the TME. Moreover, accumulating evidence suggests that Th cells are essential to the development of the immune response and are involved in the response to antitumor immunotherapy ( Basu et al, 2021 ; Renaude et al, 2021 ). T helper 1 (Th1) and T helper 2 (Th2) cells are the two predominant subtypes of CD4 + Th cells.…”

Section: Discussionmentioning

confidence: 99%

“…Th1 cells play an antitumor role by orchestrating immunity against tumor cells. Th1 cells enhance the generation and function of CD8 + T cells, prevent angiogenesis, promote the senescence of tumor cells, and protect effector cytotoxic T lymphocytes from exhaustion; thus, modulating the Th1 cell response may lead to effective immune-based therapy ( Basu et al, 2021 ; Laba et al, 2021 ; Renaude et al, 2021 ). Following differentiation, Th2 cells can produce IL-4, IL-5, IL-10, IL-13, and IL-17, not all of which are beneficial in cancer and contribute to tumor growth and metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…Following differentiation, Th2 cells can produce IL-4, IL-5, IL-10, IL-13, and IL-17, not all of which are beneficial in cancer and contribute to tumor growth and metastasis. Simultaneously, infiltration of Th2 cells in the TME is usually connected with a poor prognosis in human cancers ( Basu et al, 2021 ; Laba et al, 2021 ; Renaude et al, 2021 ). In the present study, we found that HSF2 expression was negatively associated with the infiltration level of Th1 cells but positively correlated with the level of infiltrating Th2 cells in most tumor types.…”

Section: Discussionmentioning

confidence: 99%

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Pan-Cancer Integrated Analysis of HSF2 Expression, Prognostic Value and Potential Implications for Cancer Immunity

Chen

Fan

Liu

et al. 2022

Front. Mol. Biosci.

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Heat shock factor 2 (HSF2), a transcription factor, plays significant roles in corticogenesis and spermatogenesis by regulating various target genes and signaling pathways. However, its expression, clinical significance and correlation with tumor-infiltrating immune cells across cancers have rarely been explored. In the present study, we comprehensively investigated the expression dysregulation and prognostic significance of HSF2, and the relationship with clinicopathological parameters and immune infiltration across cancers. The mRNA expression status of HSF2 was analyzed by TCGA, GTEx, and CCLE. Kaplan-Meier analysis and Cox regression were applied to explore the prognostic significance of HSF2 in different cancers. The relationship between HSF2 expression and DNA methylation, immune infiltration of different immune cells, immune checkpoints, tumor mutation burden (TMB), and microsatellite instability (MSI) were analyzed using data directly from the TCGA database. HSF2 expression was dysregulated in the human pan-cancer dataset. High expression of HSF2 was associated with poor overall survival (OS) in BRCA, KIRP, LIHC, and MESO but correlated with favorable OS in LAML, KIRC, and PAAD. The results of Cox regression and nomogram analyses revealed that HSF2 was an independent factor for KIRP, ACC, and LIHC prognosis. GO, KEGG, and GSEA results indicated that HSF2 was involved in various oncogenesis- and immunity-related signaling pathways. HSF2 expression was associated with TMB in 9 cancer types and associated with MSI in 5 cancer types, while there was a correlation between HSF2 expression and DNA methylation in 27 types of cancer. Additionally, HSF2 expression was correlated with immune cell infiltration, immune checkpoint genes, and the tumor immune microenvironment in various cancers, indicating that HSF2 could be a potential therapeutic target for immunotherapy. Our findings revealed the important roles of HSF2 across different cancer types.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Pan-Cancer Integrated Analysis of HSF2 Expression, Prognostic Value and Potential Implications for Cancer Immunity

Chen

Fan

Liu

et al. 2022

Front. Mol. Biosci.

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“…The current challenge consists of modulating CD4 + T cell polarization and promoting appropriate antitumor CD4 + helper T cell recruitment within the tumor. Given the important role of epigenetics on CD4 + T cell differentiation and plasticity, help can be exploited at this level to overcome immunotherapy failure [ 235 ]. In murine models, Goswami et al have reported that genetic depletion of EZH2 and its pharmacological inhibition using CPI-1505 resulted in phenotypic and functional alterations of Tregs as well as increased infiltration of Th1 and cytotoxic effector T cells.…”

Section: Prospects Of Combining Therapies For Cd4 + T Cell Harnessingmentioning

confidence: 99%

Harnessing Antitumor CD4+ T Cells for Cancer Immunotherapy

Khelil

Godet

Abdeljaoued

et al. 2022

Cancers

Self Cite

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Over the past decades, CD4+ T cells have been considered as a supporting actor in the fields of cancer immunotherapy. Until recently, accumulating evidence has demonstrated the critical role of CD4+ T cells during antitumor immunity. CD4+ T cells can either suppress or promote the antitumor cytotoxic CD8+ T cell responses, either in secondary lymphoid organs or in the tumor. In this review, we provide an overview of the multifaceted role of different CD4+ T cell subsets in cancer immune response and their contribution during cancer therapies. Specifically, we focus on the latest progress regarding the impact of CD4+ T cell modulation on immunotherapies and other cancer therapies and discuss the prospect for harnessing CD4+ T cells to control tumor progression and prevent recurrence in patients.

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“…The reversible function of epigenetic modification is due to the presence of enzymes that catalyze the apposition of posttranslational regulation, including histone methyltransferases and histone acetylases, which are recognized as epigenetic writers, and enzymes that act in the demethylation and deacetylation of histones, which are considered as epigenetic erasers ( Renaude et al, 2021 ). A group of DNMTs (DNMT3a, DNMT3b, and DNMT1 are dominant) function in the establishment and maintenance of DNA methylation patterns in mammals.…”

Section: Overview Of Dna Methylationmentioning

confidence: 99%

Insights Into the Role of DNA Methylation in Immune Cell Development and Autoimmune Disease

Wang

et al. 2021

Front. Cell Dev. Biol.

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To date, nearly 100 autoimmune diseases have been an area of focus, and these diseases bring health challenges to approximately 5% of the population worldwide. As a type of disease caused by tolerance breakdown, both environmental and genetic risk factors contribute to autoimmune disease development. However, in most cases, there are still gaps in our understanding of disease pathogenesis, diagnosis, and treatment. Therefore, more detailed knowledge of disease pathogenesis and potential therapies is indispensable. DNA methylation, which does not affect the DNA sequence, is one of the key epigenetic silencing mechanisms and has been indicated to play a key role in gene expression regulation and to participate in the development of certain autoimmune diseases. Potential epigenetic regulation via DNA methylation has garnered more attention as a disease biomarker in recent years. In this review, we clarify the basic function and distribution of DNA methylation, evaluate its effects on gene expression and discuss related key enzymes. In addition, we summarize recent aberrant DNA methylation modifications identified in the most important cell types related to several autoimmune diseases and then provide potential directions for better diagnosing and monitoring disease progression driven by epigenetic control, which may broaden our understanding and contribute to further epigenetic research in autoimmune diseases.

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Epigenetic Reprogramming of CD4+ Helper T Cells as a Strategy to Improve Anticancer Immunotherapy

Cited by 21 publications

References 125 publications

Pan-Cancer Integrated Analysis of HSF2 Expression, Prognostic Value and Potential Implications for Cancer Immunity

Pan-Cancer Integrated Analysis of HSF2 Expression, Prognostic Value and Potential Implications for Cancer Immunity

Harnessing Antitumor CD4+ T Cells for Cancer Immunotherapy

Insights Into the Role of DNA Methylation in Immune Cell Development and Autoimmune Disease

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