Regulating the regulatory T cells as cell therapies in autoimmunity and cancer.

Regulatory T cells (Tregs), possess a pivotal function in the maintenance of immune homeostasis. The dysregulated activity of Tregs has been associated with the onset of autoimmune diseases and cancer. Hence, Tregs are promising targets for interventions aimed at steering the immune response toward the desired path, either by augmenting the immune system to eliminate infected and cancerous cells or by dampening it to curtail the damage to self-tissues in autoimmune disorders. The activation of Tregs has been observed to have a potent immunosuppressive effect against T cells that respond to self-antigens, thus safeguarding our body against autoimmunity. Therefore, promoting Treg cell stability presents a promising strategy for preventing or managing chronic inflammation that results from various autoimmune diseases. On the other hand, Tregs have been found to be overactivated in several forms of cancer, and their role as immune response regulators with immunosuppressive properties poses a significant impediment to the successful implementation of cancer immunotherapy. However, the targeting of Tregs in a systemic manner may lead to the onset of severe inflammation and autoimmune toxicity. It is imperative to develop more selective methods for targeting the function of Tregs in tumors. In this review, our objective is to elucidate the function of Tregs in tumors and autoimmunity while also delving into numerous therapeutic strategies for reprogramming their function. Our focus is on reprogramming Tregs in a highly activated phenotype driven by the activation of key surface receptors and metabolic reprogramming. Furthermore, we examine Treg-based therapies in autoimmunity, with a specific emphasis on Chimeric Antigen Receptor (CAR)-Treg therapy and T-cell receptor (TCR)-Treg therapy. Finally, we discuss key challenges and the future steps in reprogramming Tregs that could lead to the development of novel and effective cancer immunotherapies.

Paper-based biosensors as point-of-care diagnostic devices for the detection of cancers: a review of innovative techniques and clinical applications.

The development and rapid progression of cancer are major social problems. Medical diagnostic techniques and smooth clinical care of cancer are new necessities that must be supported by innovative diagnostic methods and technologies. Current molecular diagnostic tools based on the detection of blood protein markers are the most common tools for cancer diagnosis. Biosensors have already proven to be a cost-effective and accessible diagnostic tool that can be used where conventional laboratory methods are not readily available. Paper-based biosensors offer a new look at the world of analytical techniques by overcoming limitations through the creation of a simple device with significant advantages such as adaptability, biocompatibility, biodegradability, ease of use, large surface-to-volume ratio, and cost-effectiveness. In this review, we covered the characteristics of exosomes and their role in tumor growth and clinical diagnosis, followed by a discussion of various paper-based biosensors for exosome detection, such as dipsticks, lateral flow assays (LFA), and microfluidic paper-based devices (µPADs). We also discussed the various clinical studies on paper-based biosensors for exosome detection.

Glioblastoma as a Novel Drug Repositioning Target: Updated State.

Glioblastoma multiforme (GBM) is an aggressive form of adult brain tumor that can arise from a low-grade astrocytoma. In recent decades, several new conventional therapies have been developed that have significantly improved the prognosis of patients with GBM. Nevertheless, most patients have a limited long-term response to these treatments and survive < 1 year. Therefore, innovative anti-cancer drugs that can be rapidly approved for patient use are urgently needed. One way to achieve accelerated approval is drug repositioning, extending the use of existing drugs for new therapeutic purposes, as it takes less time to validate their biological activity as well as their safety in preclinical models. In this review, a comprehensive analysis of the literature search was performed to list drugs with antiviral, antiparasitic, and antidepressant properties that may be effective in GBM and their putative anti-tumor mechanisms in GBM cells.

Current Status and Challenges of Vaccination Therapy for Glioblastoma.

Glioblastoma (GBM), also known as grade IV astrocytoma, is the most common and deadly type of central nervous system malignancy in adults. Despite significant breakthroughs in current GBM treatments such as surgery, radiotherapy, and chemotherapy, the prognosis for late-stage glioblastoma remains bleak due to tumor recurrence following surgical resection. The poor prognosis highlights the evident and pressing need for more efficient and targeted treatment. Vaccination has successfully treated patients with advanced colorectal and lung cancer. Therefore, the potential value of using tumor vaccines in treating glioblastoma is increasingly discussed as a monotherapy or in combination with other cellular immunotherapies. Cancer vaccination includes both passive administration of monoclonal antibodies and active vaccination procedures to activate, boost, or bias antitumor immunity against cancer cells. This article focuses on active immunotherapy with peptide, genetic (DNA, mRNA), and cell-based vaccines in treating GBM and reviews the various treatment approaches currently being tested. Although the ease of synthesis, relative safety, and ability to elicit tumor-specific immune responses have made these vaccines an invaluable tool for cancer treatment, more extensive cohort studies and better guidelines are needed to improve the efficacy of these vaccines in anti-GBM therapy.

TRIM8: a double-edged sword in glioblastoma with the power to heal or hurt.

Glioblastoma multiforme (GBM) is an aggressive primary brain tumor and one of the most lethal central nervous system tumors in adults. Despite significant breakthroughs in standard treatment, only about 5% of patients survive 5 years or longer. Therefore, much effort has been put into the search for identifying new glioma-associated genes. Tripartite motif-containing (TRIM) family proteins are essential regulators of carcinogenesis. TRIM8, a member of the TRIM superfamily, is abnormally expressed in high-grade gliomas and is associated with poor clinical prognosis in patients with glioma. Recent research has shown that TRIM8 is a molecule of duality (MoD) that can function as both an oncogene and a tumor suppressor gene, making it a "double-edged sword" in glioblastoma development. This characteristic is due to its role in selectively regulating three major cellular signaling pathways: the TP53/p53-mediated tumor suppression pathway, NFKB/NF-κB, and the JAK-STAT pathway essential for stem cell property support in glioma stem cells. In this review, TRIM8 is analyzed in detail in the context of GBM and its involvement in essential signaling and stem cell-related pathways. We also discuss the basic biological activities of TRIM8 in macroautophagy/autophagy, regulation of bipolar spindle formation and chromosomal stability, and regulation of chemoresistance, and as a trigger of inflammation.

Emerging insights into keratin 7 roles in tumor progression and metastasis of cancers.

Keratin 7 (KRT7), also known as cytokeratin-7 (CK-7) or K7, constitutes the principal constituent of the intermediate filament cytoskeleton and is primarily expressed in the simple epithelia lining the cavities of the internal organs, glandular ducts, and blood vessels. Various pathological conditions, including cancer, have been linked to the abnormal expression of KRT7. KRT7 overexpression promotes tumor progression and metastasis in different human cancers, although the mechanisms of these processes caused by KRT7 have yet to be established. Studies have indicated that the suppression of KRT7 leads to rapid regression of tumors, highlighting the potential of KRT7 as a novel candidate for therapeutic interventions. This review aims to delineate the various roles played by KRT7 in the progression and metastasis of different human malignancies and to investigate its prognostic significance in cancer treatment. Finally, the differential diagnosis of cancers based on the KRT7 is emphasized.

Neutrophil mediated drug delivery for targeted glioblastoma therapy: A comprehensive review.

Glioblastoma is the most common brain cancer in adults and presents a major challenge for targeted drug delivery due to the blood-brain barrier (BBB) and the highly infiltrative growth of the glioma cells into the brain. Cell-mediated drug-delivery systems have been proposed as a potential strategy to enhance the effects of drugs and reduce their side effects in the treatment of cancer. Neutrophils are the most abundant type of WBC in humans and can overcome impermeable barriers and transport drugs into inflamed sites such as tumors. Therefore, a promising approach for an innovative drug delivery system is the use of neutrophils as Trojan horses for drug delivery. However, compared to other leukocytes such as macrophages, little is known about how human neutrophils respond to and take up synthetic particles. In this review, we summarize the factors affecting the uptake of nanoparticles (NPs) by neutrophils, as well as recent advances and challenges related to the interaction between neutrophils and NPs, with particular emphasis on the interaction of magnetic mesoporous silica NPs, liposomes, albumin NPs, and PLGA NPs with neutrophils. Finally, the potential application of neutrophil-based drug delivery systems for the prevention of glioblastoma recurrence and also the potential application of neutrophil-mimicking nanoparticles (NM-NPs) in glioblastoma therapy are discussed.

Natural killer cell immunotherapy in glioblastoma.

Glioblastoma (GBM) is one of the most difficult cancers to treat because GBM has the high therapeutic resistance. Recently, immunotherapies for GBM have been used instead of conventional treatments. Among them, Natural killer (NK) cell-based immunotherapy has the potential to treat GBM due to its properties such as the absence of restriction by antigen-antibody reaction and deep penetration into the tumor microenvironment. Especially, genetically engineered NK cells, such as chimeric antigen receptor (CAR)-NK cells, dual antigen-targeting CAR NK cells, and adapter chimeric antigen receptor NK cells are considered to be an important tool for GBM immunotherapy. Therefore, this review describes the recent efforts of NK cell-based immunotherapy in GBM patients. We also describe key receptors expressing on NK cells such as killer cell immunoglobulin-like receptor, CD16, and natural killer group 2, member D (NKG2DL) receptor and discuss the function and importance of these molecules.

The immunosuppressive role of indoleamine 2, 3-dioxygenase in glioblastoma: mechanism of action and immunotherapeutic strategies.

Glioblastoma multiforme (GBM) is a fatal brain tumor in adults with a bleak diagnosis. Expansion of immunosuppressive and malignant CD4 + FoxP3 + GITR + regulatory T cells is one of the hallmarks of GBM. Importantly, most of the patients with GBM expresses the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO). While IDO1 is generally not expressed at appreciable levels in the adult central nervous system, it is rapidly stimulated and highly expressed in response to ongoing immune surveillance in cancer. Increased levels of immune surveillance in cancer are thus related to higher intratumoral IDO expression levels and, as a result, a worse OS in GBM patients. Conversion of the important amino acid tryptophan into downstream catabolite known as kynurenines is the major function of IDO. Decreasing tryptophan and increasing the concentration of immunomodulatory tryptophan metabolites has been shown to induce T-cell apoptosis, increase immunosuppressive programming, and death of tumor antigen-presenting dendritic cells. This observation supported the immunotherapeutic strategy, and the targeted molecular therapy that suppresses IDO1 activity. We review the current understanding of the role of IDO1 in tumor immunological escape in brain tumors, the immunomodulatory effects of its primary catabolites, preclinical research targeting this enzymatic pathway, and various issues that need to be overcome to increase the prospective immunotherapeutic relevance in the treatment of GBM malignancy.

Circulating non-coding RNAs as a diagnostic and management biomarker for breast cancer: current insights.

Cancer biomarkers can be used to determine the molecular status of a tumor or its metastases, which either release them directly into body fluids or indirectly through disruption of tumor/metastatic tissue. New minimally invasive and repeatable sample collection methods, such as liquid biopsy, have been developed in the last decade to apply cancer knowledge and track its progression. Circulating non-coding RNAs, which include microRNAs, long non-coding RNAs, and PIWI-interacting RNAs, are increasingly being recognized as potential cancer biomarkers. The growing understanding of cancer's molecular pathogenesis, combined with the rapid development of new molecular techniques, encourages the study of early molecular alterations associated with cancer development in body fluids. Specific genetic and epigenetic changes in circulating free RNA (cf-RNA) in plasma, serum, and urine could be used as diagnostic biomarkers for a variety of cancers. Only a subset of these cf-RNAs have been studied in breast cancer, with the most extensive research focusing on cf-miRNA in plasma. These findings pave the way for immediate use of selected cf-RNAs as biomarkers in breast cancer liquid biopsy, as well as additional research into other cf-RNAs to advance.