Publications by authors named "Yakubovich E"

Article Synopsis
  • Low intra-tumor heterogeneity (ITH) is linked to better patient survival and response to immunotherapy, but the role of immune factors in tumor aggressiveness remains unclear.
  • Researchers studied immune escape mechanisms in mouse tumors with low ITH, finding non-rejected clones had more tumor-associated macrophages and T-cell exhaustion compared to rejected ones.
  • They identified Mif as a key factor in immune rejection; knocking it out led to smaller tumors and lower macrophage infiltration, a finding that was supported by data from melanoma patients.
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While conventional wisdom initially postulated that PD-L1 serves as the inert ligand for PD-1, an emerging body of literature suggests that PD-L1 has cell-intrinsic functions in immune and cancer cells. In line with these studies, here we show that engagement of PD-L1 via cellular ligands or agonistic antibodies, including those used in the clinic, potently inhibits the type I interferon pathway in cancer cells. Hampered type I interferon responses in PD-L1-expressing cancer cells resulted in enhanced efficacy of oncolytic viruses in vitro and in vivo.

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Introduction: Epithelial ovarian cancer (OC) stands as one of the deadliest gynecologic malignancies, urgently necessitating novel therapeutic strategies. Approximately 60% of ovarian tumors exhibit reduced expression of major histocompatibility complex class I (MHC I), intensifying immune evasion mechanisms and rendering immunotherapies ineffective. NOD-like receptor CARD domain containing 5 (NLRC5) transcriptionally regulates MHC I genes and many antigen presentation machinery components.

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Targeted therapy resistance frequently develops in melanoma due to intratumor heterogeneity and epigenetic reprogramming. This also typically induces cross-resistance to immunotherapies. Whether this includes additional modes of therapy has not been fully assessed.

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Cancer cells often metastasize by undergoing an epithelial-mesenchymal transition (EMT). Although abundance of CD8 T-cells in the tumor microenvironment correlates with improved survival, mesenchymal cancer cells acquire greater resistance to antitumor immunity in some cancers. We hypothesized the EMT modulates the immune response to ovarian cancer.

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Decreased intra-tumor heterogeneity (ITH) correlates with increased patient survival and immunotherapy response. However, even highly homogenous tumors may display variability in their aggressiveness, and how immunologic-factors impinge on their aggressiveness remains understudied. Here we studied the mechanisms responsible for the immune-escape of murine tumors with low ITH.

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Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. The disease is often diagnosed after wide-spread dissemination, and the standard treatment combines aggressive surgery with platinum-based chemotherapy; however, most patients experience relapse in the form of peritoneal carcinomatosis, resulting in a 5-year mortality below 45%. There is clearly a need for the development of novel treatments and cancer immunotherapies offering a different approach.

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Clinical trials are currently exploring combinations of PARP inhibitors and immunotherapies for the treatment of ovarian cancer, but their effects on the ovarian tumour microenvironment (TME) remain unclear. Here, we investigate how olaparib, PD-L1 monoclonal antibodies, and their combination can influence TME composition and survival of tumour-bearing mice. We further explored how BRCA deficiencies can influence the response to therapy.

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Article Synopsis
  • * The Sordariomycetes class has become a key focus, with over 3,574 sequenced species providing a wealth of data for understanding genetic and biological traits of fungi.
  • * Recent studies utilizing big data analyses have unveiled new insights into gene regulation, sexual development, and metabolic processes, moving the field beyond traditional single-species models to a broader, collaborative approach.
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Long-term maintenance of the adult neurogenic niche depends on proper regulation of entry and exit from quiescence. Neural stem cell (NSC) transition from quiescence to activation is a complex process requiring precise cell-cycle control coordinated with transcriptional and morphological changes. How NSC fate transitions in coordination with the cell-cycle machinery remains poorly understood.

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Article Synopsis
  • Epithelial ovarian cancer (EOC) is the deadliest gynecologic cancer, with a need for better treatment options, particularly since current immunotherapy has limited effectiveness, benefiting less than 15% of patients.
  • Researchers investigated six different ovarian tumor models to understand their varying immune responses, employing techniques like single-cell RNA sequencing and flow cytometry.
  • These models, showcasing different origins and mutations, revealed that certain tumors had high T cell infiltration, while others had predominant macrophage presence, highlighting the diversity of immune environments and their potential as tools for developing and testing new immunotherapies.
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Ovarian fibrosis is a pathological condition associated with aging and is responsible for a variety of ovarian dysfunctions. Given the known contributions of tissue fibrosis to tumorigenesis, it is anticipated that ovarian fibrosis may contribute to ovarian cancer risk. We recently reported that diabetic postmenopausal women using metformin had ovarian collagen abundance and organization that were similar to premenopausal ovaries from nondiabetic women.

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The nature of saprophytic and mycoparasitic hyphal growth of spp. has been studied extensively, yet its initiation via conidial germination in this genus is less well understood. Using near-synchronous germinating cultures of , we followed the morphological progression from dormant conidia to initial polar growth to germling formation and to evidence for first branching.

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Exosomes, the subclass of small membrane extracellular vesicles, have great diagnostic and therapeutic potential, but the lack of standardized methods for their efficient isolation and analysis limits the introduction of exosomal technologies into clinical practice. This review discusses the problems associated with the isolation of exosomes from biological fluids, as well as the principles of traditional and alternative methods of isolation. The aim of the presented review is to illustrate the variety of approaches based on the physical and biochemical properties of exosomes that can be used for exosome isolation.

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