Project description:Extracellular vesicles (EVs) are membrane-coated particles secreted by virtually all cell types in response to different stimuli, both in physiological and pathological conditions. Their content generally reflects their biological functions and includes a variety of molecules, such as nucleic acids, proteins and cellular components. The role of EVs as signaling vehicles has been widely demonstrated. In particular, they are actively involved in the pathogenesis of several hematological malignancies (HM), mainly interacting with a number of target cells and inducing functional and epigenetic changes. In this regard, by releasing their cargo, EVs play a pivotal role in the bilateral cross-talk between tumor microenvironment and cancer cells, thus facilitating mechanisms of immune escape and supporting tumor growth and progression. Recent advances in high-throughput technologies have allowed the deep characterization and functional interpretation of EV content. In this review, the current knowledge on the high-throughput technology-based characterization of EV cargo in HM is summarized.
Project description:Tumor immune tolerance remains a major barrier for effective anti-cancer therapy. A growing number of pathways whereby solid tumors escape immune surveillance have been characterized (1). This progress led us to revisit the "hallmarks of cancer" and brought forward many promising immunotherapies. Every growing bodies of research have brought forward many exciting treatment strategies for hematological cancers like chimeric antigen receptor T cells (CAR-T cells) and immune checkpoint inhibitors. Given the distinct characteristics of the different cancers, some benefited profoundly from such therapies while some remain challenging for scientists and physicians. Here, we discuss the unique aspect of hematological malignancies, and briefly review the history, existing and future of immunotherapies for this group of cancer.
Project description:Telomerase expression and telomere maintenance are critical for cell proliferation and survival, and they play important roles in development and cancer, including hematological malignancies. Transcriptional regulation of the rate-limiting subunit of human telomerase reverse transcriptase gen (hTERT) is a complex process, and unveiling the mechanisms behind its reactivation is an important step for the development of diagnostic and therapeutic applications. Here, we review the main mechanisms of telomerase activation and the associated hematologic malignancies.
Project description:The role of the WNT signaling pathway in key cellular processes, such as cell proliferation, differentiation and migration is well documented. WNT signaling cascade is initiated by the interaction of WNT ligands with receptors belonging to the Frizzled family, and/or the ROR1/ROR2 and RYK families. The downstream signaling cascade results in the activation of the canonical ?-catenin dependent pathway, ultimately leading to transcriptional control of cell proliferation, or the non-canonical pathway, mainly acting on cell migration and cell polarity. The high level of expression of both WNT ligands and WNT receptors in cancer cells and in the surrounding microenvironment suggests that WNT may represent a central conduit of interactions between tumor cells and microenviroment. In this review we will focus on WNT pathways deregulation in hematological cancers, both at the ligand and receptor levels. We will review available literature regarding both the classical ?-catenin dependent pathway as well as the non-canonical pathway, with particular emphasis on the possible exploitation of WNT aberrant activation as a therapeutic target, a notion supported by preclinical data.