Search

Histone methyltransferases (HMTs) are enzymes that regulate histone methylation and play an important role in controlling transcription by altering the chromatin structure. Aberrant activation of HMTs has been widely reported in certain types of neoplastic cells. Among them, G9a/EHMT2 and GLP/EHMT1 are crucial for H3K9 methylation, and their dysregulation has been associated with tumor initiation and progression in different types of cancer. More recently, it has been shown that G9a and GLP appear to play a critical role in several lymphoid hematologic malignancies. Importantly, the key roles played by both enzymes in various diseases made them attractive targets for drug development. In fact, in recent years, several groups have tried to develop small molecule inhibitors targeting their epigenetic activities as potential anticancer therapeutic tools. In this review, we discuss the physiological role of GLP and G9a, their oncogenic functions in hematologic malignancies of the lymphoid lineage, and the therapeutic potential of epigenetic drugs targeting G9a/GLP for cancer treatment., (© 2024. The Author(s).)

Among the various biological properties presented by Mesenchymal Stem Cells (MSCs), their ability to control the immune response and fight pathogen infection through the production of antimicrobial peptides (AMPs) have been the subject of intense research in recent years. AMPs secreted by MSCs exhibit activity against a wide range of microorganisms, including bacteria, fungi, yeasts, and viruses. The main AMPs produced by these cells are hepcidin, cathelicidin LL-37, and β-defensin-2. In addition to acting against pathogens, those AMPs have also been shown to interact with MSCs to modulate MSC proliferation, migration, and regeneration, indicating that such peptides exert a more diverse biological effect than initially thought. In the present review, we discuss the production of AMPs by MSCs, revise the multiple functions of these peptides, including their influence over MSCs, and present an overview of clinical situations in which the antimicrobial properties of MSCs may be explored for therapy. Finally, we discuss possibilities of combining MSCs and AMPs to generate improved therapeutic strategies., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The development of immunotherapeutic approaches for the treatment of melanoma requires a better understanding of immunoescape mechanisms of tumor cells and how they interact with other tumor-resident cell types. Here, we evaluated how the conditioned media of resting (rCM) and immune-activated PBMCs (iCM) influence the ability of a metastatic melanoma cell line (MeWo) to control T-cells function. MeWo cells were expanded in RPMI, rCM, or iCM and the secretome generated after cell expansion was identified as MeSec (RPMI), niSec (non-inflammatory), or iSec (inflammatory secretome), respectively. Then, the immunomodulatory potential of such secretomes was tested in PHA-activated PBMCs. iCM induced higher levels of IFN-γ and IL-10 in treated melanoma cells compared to rCM, as well as higher IDO and PD-L1 expression. The iSec was able to inhibit T-cell activation and proliferation. Interestingly, PBMCs treated with iSec presented a reduced expression of the regulators of Th1 and Th2 responses T-BET and GATA-3 , as well as low expression of IFN-γ , and co-stimulatory molecules TIM-3 and LAG-3 . Importantly, our findings show that melanoma may benefit from an inflammatory microenvironment to enhance its ability to control the T-cell response. Interestingly, such an immunomodulatory effect involves the inhibition of the checkpoint molecules LAG-3 and TIM-3 , which are currently investigated as important therapeutic targets for melanoma treatment. Further studies are needed to better understand how checkpoint molecules are modulated by paracrine and cell contact-dependent interaction between melanoma and immune cells. Such advances are fundamental for the development of new therapeutic approaches focused on melanoma immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bogéa, Silva-Carvalho, Filiú-Braga, Neves and Saldanha-Araujo.)