Tumor microenvironment

Pharmacological activation of the retinoic acid-inducible gene I (RIG-I) pathway holds promise for increasing tumor immunogenicity and improving the response to immune checkpoint inhibitors (ICIs). However, the potency and clinical efficacy of 5'-triphosphate RNA (3pRNA) agonists of RIG-I are hindered by multiple pharmacological barriers, including poor pharmacokinetics, nuclease degradation, and inefficient delivery to the cytosol where RIG-I is localized. Here, we address these challenges through the design and evaluation of ionizable lipid nanoparticles (LNPs) for the delivery of 3p-modified stem-loop RNAs (SLRs)...

The efficient delivery of therapeutic proteins to tumor sites is a promising cancer treatment modality. Hydrogen-bonded organic frameworks (HOFs) have been successfully used for the protective encapsulation of proteins; however, easy precipitation and lack of controlled release of existing HOFs limit their further application for protein delivery in vivo. In this study, a hypoxia-responsive HOF, self-assembled from azobenzenedicarboxylate/polyethylene glycol-conjugated azobenzenedicarboxylate and tetrakis(4-amidiniumphenyl)methane through charge-assisted hydrogen-bonding, is developed for systemic protein delivery to tumor cells...

Gliomas, the most prevalent primary brain tumors, pose considerable challenges due to their heterogeneity, intricate tumor microenvironment (TME), and blood-brain barrier (BBB), which restrict the effectiveness of traditional treatments like surgery and chemotherapy. This review provides an overview of engineered cell membrane technologies in glioma therapy, with a specific emphasis on targeted drug delivery and modulation of the immune microenvironment. This study investigates the progress in engineered cell membranes, encompassing physical, chemical, and genetic alterations, to improve drug delivery across the BBB and effectively target gliomas...

CD8+ T cell dysfunction impedes anti-tumor immunity in solid cancers but the underlying mechanisms are diverse and poorly understood. Extracellular matrix (ECM) composition has been linked to impaired T cell migration and enhanced tumor progression; however, impacts of individual ECM molecules on T cell function in the tumor microenvironment (TME) are only beginning to be elucidated. Upstream regulators of aberrant ECM deposition and organization in solid tumors are equally ill-defined. Therefore, we investigated how ECM composition modulates CD8+ T cell function in undifferentiated pleomorphic sarcoma (UPS), an immunologically active desmoplastic tumor...

Scientific knowledge of cancer has advanced greatly throughout the years, with most recent studies findings includes many hallmarks that capture disease's multifaceted character. One of the novel approach utilized for the delivery of anti-cancer agents includes mesenchymal stem cell mediated drug delivery. Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells that may be extracted from bone marrow, tooth pulp, adipose tissue and placenta/umbilical cord blood dealing with adult stem cells. MSCs are mostly involved in regeneration of tissue, they have also been shown to preferentially migrate to location of several types of tumor in-vivo ...

Ferroptosis is a form of intracellular iron-dependent cell death that differs from necrosis, autophagy and apoptosis. Intracellular iron mediates Fenton reaction resulting in lipid peroxidation production, which in turn promotes cell death. Although cancer cell exhibit's ability to escape ferroptosis by multiple pathways such as SLC7A11, GPX4, induction of ferroptosis could inhibit cancer cell proliferation, migration and invasion. In tumor microenvironment, ferroptosis could affect immune cell (T cells, macrophages etc...

PURPOSE: A strong immunosuppressive tumor microenvironment (TME) represents the major barrier responsible for the failure of current immunotherapy approaches in treating Glioblastoma Multiforme (GBM). Within the TME, the regulatory T cells (Tregs) exert immunosuppressive effects on CD8+ T cell - mediated anti-cancer immune killing. Consequently, targeting and inhibiting their immunosuppressive function emerges as an effective therapeutic strategy for GBM. The present study aimed to investigate the mechanisms and effects of Suberanilohydroxamic Acid (SAHA), a histone deacetylase inhibitor, on immunosuppressive Tregs...

Immunotherapy has revolutionized the treatment of tumors, but there are still a large number of patients who do not benefit from immunotherapy. Pericytes play an important role in remodeling the immune microenvironment. However, how pericytes affect the prognosis and treatment resistance of tumors is still unknown. This study jointly analyzed single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing data of multiple cancers to reveal pericyte function in the colorectal cancer microenvironment. Analyzing over 800 000 cells, it was found that colorectal cancer had more pericyte enrichment in tumor tissues than other cancers...

PURPOSE: The overall survival rate for metastatic osteosarcoma hovers around 20%. Responses to second-line chemotherapy, targeted therapies, and immunotherapies have demonstrated limited efficacy in metastatic osteosarcoma. Our objective is to validate differentially expressed genes and signaling pathways between non-metastatic and metastatic osteosarcoma, employing single-cell RNA sequencing (scRNA-seq) and additional functional investigations. We aim to enhance comprehension of metastatic mechanisms and potentially unveil a therapeutic target...

Chimeric Antigen Receptor T cell (CAR-T) therapy has revolutionized cancer treatment, but its application to solid tumors is limited. CAR-T cells have poor incapability of entering, surviving, proliferating, and finally exerting function in the tumor microenvironment. This review summarizes the main strategies related to enhancing the infiltration, efficacy, antigen recognition, and production of CAR-T in solid tumors. Additional applications of CAR-γδ T and macrophages are also discussed. We believe CAR-T will be a milestone in treating solid tumors once these problems are solved...

BACKGROUND: Neoadjuvant and adjuvant immunotherapies for cancer have evolved through a series of remarkable and critical research advances; however, addressing their similarities and differences is imperative in clinical practice. Therefore, this study aimed to examine their similarities and differences from the perspective of informatics analysis. METHODS: This cross-sectional study retrospectively analyzed extensive relevant studies published between 2014 and 2023 using stringent search criteria, excluding non-peer-reviewed and non-English documents...

Forkhead box protein 1 (FOXP1) serves as a tumour promoter or suppressor depending on different cancers, but its effect in oesophageal squamous cell carcinoma has not been fully elucidated. This study investigated the role of FOXP1 in oesophageal squamous cell carcinoma through bioinformatics analysis and experimental verification. We determined through public databases that FOXP1 expresses low in oesophageal squamous cell carcinoma compared with normal tissues, while high expression of FOXP1 indicates a better prognosis...

Tumour immune microenvironment (TIME) plays an indispensable role in tumour progression, and tumour-associated macrophages (TAMs) are the most abundant immune cells in TIME. Non-apoptotic regulated cell death (RCD) can avoid the influence of tumour apoptosis resistance on anti-tumour immune response. Specifically, autophagy, ferroptosis, pyroptosis and necroptosis mediate the crosstalk between TAMs and tumour cells in TIME, thus reprogram TIME and affect the progress of tumour. In addition, although some achievements have been made in immune checkpoint inhibitors (ICIs), there is still defect that ICIs are only effective for some people because non-apoptotic RCD can bypass the apoptosis resistance of tumour...

CD39 is the rate-limiting enzyme for the molecular signal cascade leading to the generation of ADP and adenosine monophosphate (AMP). In conjunction with CD73, CD39 converts adenosine triphosphate (ATP) to ADP and AMP, which leads to the accumulation of immunosuppressive adenosine in the tumor microenvironment. This review focuses on the role of CD39 and CD73 in immune response and malignant progression, including the expression of CD39 within the tumor microenvironment and its relationship to immune effector cells, and its role in antigen presentation...

The laminar flow profiles in microfluidic systems coupled to rapid diffusion at flow streamlines have been widely utilized to create well-controlled chemical gradients in cell cultures for spatially directing cell migration. However, within hydrogel-based closed microfluidic systems of limited depth (≤0.1 mm), the biomechanical cues for the cell culture are dominated by cell interactions with channel surfaces rather than with the hydrogel microenvironment. Also, leaching of poly(dimethylsiloxane) (PDMS) constituents in closed systems and the adsorption of small molecules to PDMS alter chemotactic profiles...

The primary treatment for glioblastoma (GBM) is removing the tumor mass as defined by magnetic resonance imaging (MRI). However, MRI has limited diagnostic and predictive value. Tumor-associated macrophages (TAMs) are abundant in GBM microenvironment (TME) and are found in peripheral blood (PB). FKBP51 expression, with its canonical and spliced isoforms, is constitutive in immune cells and aberrant in GBM. Spliced FKBP51s supports M2-polarization. To find an immunological signature that combined with MRI could advance in diagnosis, we immunophenotyped the macrophages of TME and PB from 37 GBM patients using FKBP51s and classical M1-M2 markers...

BACKGROUND: About 75% of medullary thyroid cancers (MTCs) are sporadic with 45-70% being driven by a RET mutation. Selpercatinib is an approved treatment for RET-mutated (mutRET) MTC, however, treatments are needed for wild-type RET MTC (wtRET). Genomic alterations and transcriptomic signatures of wtRET MTC may reveal new therapeutic insights. METHODS: We did a retrospective analysis of MTC samples submitted for DNA/RNA sequencing and PD-L1 expression using IHC at a CLIA/CAP-certified lab...

Hepatocellular carcinoma is one of the most common cancers worldwide. Despite progress in treatment, recurrence after radical treatment is common, and the prognosis remains poor for patients with advanced disease. Therefore, there is a need to identify prognostic and predictive factors for the response to therapy or more intensive surveillance or treatment. Because the tumor microenvironment plays a crucial role in the development of cancer and metastasis, it is a crucial need to understand processes that are involved in carcinogenesis...

"Transition" metal-coordinated plant polyphenols are a type of promising antitumor nanodrugs owing to their high biosafety and catalytic therapy potency; however, the major obstacle restricting their clinical application is their poor tumor accumulation. Herein, Fe-doped ZIF-8 was tailored using tannic acid (TA) into a hollow mesoporous nanocarrier for gallic acid (GA) loading. After hyaluronic acid (HA) modification, the developed nanosystem of HFZIF-8/GA@HA was used for the targeted delivery of Fe ions and GA, thereby intratumorally achieving the synthesis of an Fe-GA coordinated complex...

Cancer drug testing in animals is an extremely poor predictor of the drug's safety and efficacy observed in humans. Hence there is a pressing need for functional testing platforms that better predict traditional and immunotherapy responses in human, live tumor tissue or tissue constructs, and at the same time are compatible with the use of mouse tumor tissue to facilitate building more accurate disease models. Since many cancer drug actions rely on mechanisms that depend on the tumor microenvironment (TME), such platforms should also retain as much of the native TME as possible...