The pivotal influence of immune subpopulation functional and phenotypic states on the response to immune checkpoint therapy (ICT) is underscored by the role of epigenetic mechanisms driving cellular plasticity. With the comprehensive characterization of the epigenetic machinery's role in governing cancer cell plasticity, Creative Biolabs has identified the exploration of epigenetic regulation within immune subsets, particularly in the context of ICT, as a burgeoning research frontier.
Fig. 1 Epigenetic insights into the tumor microenvironment: implications for cancer immunotherapy.1
Harnessing epigenetic modifications to modulate tumor-associated immune responses holds substantial promise as a therapeutic avenue for cancer patients. For instance, the administration of a monoclonal antibody targeting CTLA-4 has been shown to induce the expression of EZH2, a pivotal epigenetic enzyme involved in cellular plasticity. CD28 signaling, in turn, leads to heightened EZH2 expression in T cells. The augmentation of CD28 signaling by anti-CTLA-4 amplifies EZH2 expression in T cells. Building upon these findings, a series of preclinical investigations were devised, revealing a potential role for EZH2 in driving adaptive resistance to anti-CTLA-4 therapy. Combining EZH2 inhibition with anti-CTLA-4 therapy resulted in enhanced survival in preclinical studies. These findings serve as the basis for a clinical trial exploring the rational combination of an EZH1/2 inhibitor with an anti-CTLA-4 antibody in patients with genitourinary malignancies exhibiting primary resistance to ICT. This represents merely a glimpse into the extensive realm of epigenetic regulation of immune cells, laying the groundwork for synergistic combinations of epigenetic modulators with ICT.
 Fig. 2 Targeting epigenetic memory in microglial response for therapeutic strategies.2 |
This study highlights the indispensability of epigenetic mechanisms in orchestrating the polarization, activation, and formation of memory in microglial cells. The strategic manipulation of epigenetic factors in these processes could offer a potential avenue to attenuate the advancement of neurodegenerative and neuroinflammatory disorders. |
 Fig. 3 Interplay of epigenetic regulation and innate immunity in the battle against infection.3 |
Epigenetic regulation encompasses a spectrum of mechanisms, including DNA modifications, post-translational modifications (PTMs) of histones, chromatin remodeling, and the involvement of non-coding RNAs (ncRNAs), all operating in a coordinated fashion. This multifaceted epigenetic regulation plays a central role in shaping chromatin states and gene expression patterns, both within the host and the pathogen. On one hand, it orchestrates immune homeostasis to facilitate the innate immune responses of the host against the pathogen, while, on the other hand, it facilitates immune evasion by the pathogen. |
 Fig. 4 Evolution of genetic and epigenetic alterations in cancer.4 |
Chromatin and its associated epigenetic mechanisms serve to stabilize gene expression and cellular states, enabling the appropriate responses to developmental or environmental signals. However, genetic, environmental, or metabolic stressors can lead to epigenetic landscapes that become excessively constrictive or permissive, thereby contributing to the onset of diseases, including cancer. Restrictive chromatin states may impede the activation of tumor suppressor programs or hinder cellular differentiation. This review comprehensively examines the expansive roles of epigenetic abnormalities in the initiation and progression of tumors, highlighting their potential to give rise to the hallmark features of cancer. |
Creative Biolabs coupled with extensive technological proficiency and state-of-the-art instrumentation, is committed to providing an expansive array of services in immune checkpoint development. These services encompass antibodies, proteins, peptides, assays, small molecule drugs, and an assortment of offerings. Such as Biomarker Development for Immune Checkpoint Inhibitor (ICI), Immune Checkpoint Assays, and Preclinical Research for Immune Checkpoint Targeting Drugs. Our adept team is also poised to streamline the process and save you time by delivering tailored customer service to align with your precise requirements. For details, please do not hesitate to contact us.
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