The development of advanced biological models like microphysiological systems, able to rebuild the complexity of the physiological and/or pathological environments at a single-cell detail level in an in-vivo-like approach, is proving to be a promising tool to understand the mechanisms of interactions between different cell populations and main features of several diseases. In this frame, the tumor-immune microenvironment on a chip represents a powerful tool to profile key aspects of cancer progression, immune activation, and response to therapy in several immuno-oncology applications. In the present chapter, we provide a protocol to identify and characterize the time evolution of apoptosis by time-lapse fluorescence and confocal imaging in a 3D microfluidic coculture murine model including cancer and spleen cells.
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http://dx.doi.org/10.1007/978-1-0716-3593-3_9 | DOI Listing |
Ultraviolet (UV)-induced DNA mutations produce genetic drivers of cutaneous melanoma initiation and numerous neoantigens that can trigger anti-tumor immune responses in the host. Consequently, melanoma cells must rapidly evolve to evade immune detection by simultaneously modulating cell-autonomous epigenetic mechanisms and tumor-microenvironment interactions. Angiogenesis has been implicated in this process; although an increase of vasculature initiates the immune response in normal tissue, solid tumors manage to somehow enhance blood flow while preventing immune cell infiltration.
View Article and Find Full Text PDFPhagocytic clearance of apoptotic cancer cells (efferocytosis) by tumor-associated macrophages (TAMs) contributes in a substantial manner to the establishment of an immunosuppressive tumor microenvironment. This puts in context our observation that the female steroid hormone 17β-estradiol (E2) facilitates tumor immune resistance through cancer cell extrinsic Estrogen Receptor (ERalpha;) signaling in TAMs. Notable was the finding that E2 induces the expression of CX3CR1 in TAMs to enable efferocytosis of apoptotic cancer cells which results in the suppression of type I interferon (IFN) signaling.
View Article and Find Full Text PDFFront Immunol
January 2025
Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Background: Squalene epoxidase (SQLE) is a key enzyme in cholesterol biosynthesis and has been shown to negatively affect tumor immunity and is associated with poor outcomes of immunotherapy in various cancers. While most research in this area has focused on the impact of cholesterol on immune functions, the influence of SQLE-mediated squalene metabolism within the tumor immune microenvironment (TIME) remains unexplored.
Methods: We established an immune-competent mouse model (C57BL/6) bearing mouse pancreatic cancer xenografts (KPC cells) with or without stable SQLE-knockdown (SQLE-KD) to evaluate the impact of SQLE-mediated metabolism on pancreatic cancer growth and immune functions.
Immunotargets Ther
December 2024
Department of Thoracic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, People's Republic of China.
In recent years, the combination of immune checkpoint inhibitors (ICIs) with antiangiogenic agents has led to significant breakthroughs in cancer treatment. Such as programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Antiangiogenic therapy plays a pivotal role in normalizing blood vessels and remodeling the tumor immune microenvironment while ICIs not only enhance the host's antitumor immune response by blocking negative regulatory signals but also promote vascular normalization.
View Article and Find Full Text PDFACS Synth Biol
January 2025
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
Bacterial outer membrane vesicles (OMVs) have emerged as promising vehicles for anticancer drug delivery due to their inherent tumor tropism, immune-stimulatory properties, and potential for functionalization with therapeutic proteins. Despite their advantages, the high lipopolysaccharide (LPS) endotoxin content in the OMVs raises significant safety and regulatory challenges. In this work, we produce LPS-attenuated and LPS-free OMVs and systematically assess the effects of LPS modification on OMVs' physicochemical characteristics, membrane protein content, immune-stimulatory capacity, tolerability, and anticancer efficacy.
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