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TSG6 affects anti cancer drug resistance and angiogenesis in 3D spheroid model of canine mammary gland tumor cells.

TSG6 (Tumor necrosis factor stimulated gene-6) plays a critical role in modulating the tumor microenvironment by regulating inflammation, immune responses, and extracellular matrix remodeling. Hypoxia affects tumor growth, angiogenesis, and anti-cancer drug resistance in the tumor microenvironment, and TSG6 expression is known to influence HIF-1α expression in tumor tissues. In this study, we created TSG6 knockdown spheroids of canine mammary gland tumor (MGT) cells (CIPp and CIPm) to investigate the effects of TSG6 on angiogenesis and drug resistance in the tumor microenvironment. Using a siR…

Transforming growth factor beta derived from bone matrix promotes cell proliferation of prostate cancer and osteoclast activation-associated osteolysis in the bone microenvironment.

Metastatic prostate tumors in the bone microenvironment stimulate bone resorption, resulting in release of growth factors from the bone matrix that play important roles in tumor growth and osteoclast induction. Transforming growth factor beta (TGFbeta) is one of the most abundantly stored cytokines in bone matrix, regulating diverse biological activities. Here we evaluate its involvement in prostate tumor growth in the bone microenvironment, comparing with tumor growth in the subcutaneous microenvironment as a control. Rat prostate tumors were transplanted onto the cranial bone and into the su

The multifaceted roles of macrophages in the transition from hepatitis to hepatocellular carcinoma: From mechanisms to therapeutic strategies.

Macrophages are central to the progression from hepatitis to hepatocellular carcinoma (HCC), with their remarkable plasticity and ability to … r stem cell maintenance, and angiogenesis. Their functional plasticity enables them to adapt to the tumor microenvironment, thereby promoting tumor progression and resistance to therapy. Targeting macrophages represents a promising strategy for preventing and treating HCC. Therapeutic approaches, including reprogramming macrophage phenotypes to enhance anti-tumor immuni …

Immunotherapy and the Combination with Targeted Therapies for Advanced Hepatocellular Carcinoma.

One of the most important abilities of a tumor is to establish a state of immunosuppression inside the tumor microenvironment. This is made possible through numerous mechanisms of tumor immune escape that have been identified in experimental studies during the last decades. In addition, the hepatic microenvironment is commonly oriented towards a state of immune tolerance because the liver receives blood from the hepatic arteries and portal veins containing a variety of endogenous antigens. Therefore, the hepatic microenvironment establishes an autoimmune tolerance, preventing an autoimmune rea…

Effects of ibrutinib on T-cell immunity in patients with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL), a highly heterogeneous B-cell malignancy, is characterized by tumor microenvironment disorder and T-cell immune dysfunction, which play a major role in the proliferation and survival of CLL cells. Ibrutinib is the first irreversible inhibitor of Bruton's tyrosine kinase (BTK). In addition to targeting B-cell receptor (BCR) signaling to kill tumor cells, increasing evidence has suggested that ibrutinib regulates the tumor microenvironment and T-cell immunity in a direct and indirect manner. For example, ibrutinib not only reverses the tumor microenvironment b…

Automatic and label-free identification of blood vessels in gliomas using the combination of multiphoton microscopy and image analysis.

Currently, the targeted treatment of tumor based on the tumor microenvironment is newly developed. Blood vessels are the key parts in the tumor microenvironment, which is taken as a new visible target for tumor therapy. Multiphoton microscopy (MPM), based on the second harmonic generation and two-photon excited fluorescence, is available to make the label-free analysis on the blood vessels in human gliomas. MPM can reveal the vascular morphological characteristics in gliomas, including vascular malformation, intense vascular proliferation, perivascular collagen deposition, perivascular lymphoc…

Next-generation CD40 agonists for cancer immunotherapy.

INTRODUCTION: There is a need for new therapies that can enhance response rates and broaden the number of cancer indications where immunotherapies provide clinical benefit. CD40 targeting therapies provide an opportunity to meet this need by promoting priming of tumor-specific T cells and reverting the suppressive tumor microenvironment. This is supported by emerging clinical evidence demonstrating the benefits of immunotherapy with CD40 antibodies in combination with standard of care chemotherapy. AREAS COVERED: This review is focused on the coming wave of next-generation CD40 agonists aimin…

Empowering therapeutic antibodies with IFN-α for cancer immunotherapy.

Type 1 IFNs stimulate secretion of IP-10 (CXCL10) which is a critical chemokine to recruit effector T cells to the tumor microenvironment and IP-10 knockout mice exhibit a phenotype with compromised effector T cell generation and trafficking. Type 1 IFNs also induce MHC class 1 upregulation on tumor cells which can enhance anti-tumor CD8 T cell effector response in the tumor microenvironment. Although type 1 IFNs show great promise in potentiating anti-tumor immune response, systemic delivery of type 1 IFNs is associated with toxicity thereby limiting clinical application. In this study, we fu…

CTSG-expressing mast cells confer resistance to immunotherapy in colorectal cancer.

BACKGROUND: Mast cells are increasingly recognized as an important regulator of the tumor microenvironment. However, their role in colorectal cancer (CRC) is controversial, and there is a lack of targetable mast cell-specific molecules to improve the tumor microenvironment and overcome resistance to immunotherapy. METHODS: We used single-cell RNA sequencing, bulk RNA sequencing, and bioinformatics analyses to characterize mast cell subsets in the CRC tumor microenvironment and assess their association with immunotherapy response. We further employed a murine orthotopic CRC model and multi-omi…

A 3D vascularized tumor spheroid microfluidic platform for head and neck cancer research: new insights.

Conventional in vitro cancer models often fail to replicate the complexity of the tumor microenvironment. We have developed a 3D micro-engineered vascularized organoid chip (VOC) platform to enhance the physiological relevance of in vivo tumor models. This platform incorporates patient-derived tumor spheroids from head and neck cancer patients, providing a more accurate simulation of the native tumor microenvironment. We evaluated the efficacy of 5-fluorouracil (5-FU) and sunitinib on angiogenic sprouting and cell viability of red fluorescent protein-expressing human umbilical vein endothelial…

Synergistic Provoking of Pyroptosis and STING Pathway by Multifunctional Manganese-Polydopamine Nano-Immunomodulator for Enhanced Renal Cell Carcinoma Immunotherapy.

Manganese ions are known to enhance anti-tumor immunity by activating the cGAS-STING signaling pathway. However, precise modulation of the tumor microenvironment using manganese ions remains a challenge. Dopamine, with its controlled release properties within the tumor microenvironment, offers significant potential for precision drug delivery systems. Metastatic renal cell carcinoma (RCC), being refractory to conventional treatments, necessitates innovative therapeutic approaches. In this study, a multifunctional manganese-polydopamine nano-immunomodulator coated with hyaluronic acid (PDA-Mn-H…

Chronic lymphocytic leukemia cells are active participants in microenvironmental cross-talk.

The importance of the tumor microenvironment in chronic lymphocytic leukemia is widely accepted. Nevertheless, the understanding of the complex interplay between the various types of bystander cells and chronic lymphocytic leukemia cells is incomplete. Numerous studies have indicated that bystander cells provide chronic lymphocytic leukemia-supportive functions, but it has also become clear that chronic lymphocytic leukemia cells actively engage in the formation of a supportive tumor microenvironment through several cross-talk mechanisms. In this review, we describe how chronic lymphocytic leu…

An adaptive immune response driven by mature, antigen-experienced T and B cells within the microenvironment of oral squamous cell carcinoma.

Lymphocyte infiltrates have been observed in the microenvironment of oral cancer; however, little is known about whether the immune response of the lymphocyte infiltrate affects tumor biology. For a deeper understanding of the role of the infiltrating-lymphocytes in oral squamous cell carcinoma (OSCC), we characterized the lymphocyte infiltrate repertoires and defined their features. Immunohistochemistry revealed considerable T and B cell infiltrates and lymphoid follicles with germinal center-like structures within the tumor microenvironment. Flow cytometry demonstrated that populations of an…

Single-cell transcriptome analysis in ovarian steroid cell tumors-not otherwise specified.

BACKGROUND: Ovarian steroid cell tumors-not otherwise specified (SCT-NOS) is a rare category of sex cord-stromal tumor, however, its pathophysiology is unclear. A comprehensive cellular atlas of ovarian SCT-NOS remains lacking. METHODS: We reported a case of a 41-year-old woman with hyperandrogenism for whom histopathological analysis confirmed the presence of ovarian SCT-NOS. This study utilized single-cell RNA sequencing in a case of ovarian SCT-NOS. RESULTS: Seven cell types, including four keratin 19 (KRT19)⁺ steroidogenic cell subtypes, were identified in the tumor microenvironment. We …

Pathological Crosstalk between Metastatic Breast Cancer Cells and the Bone Microenvironment.

Bone is the most common metastatic site in breast cancer. Upon arrival to the bone, disseminated tumor cells can undergo a period of dormancy but often eventually grow and hijack the bone microenvironment. The bone marrow microenvironment consists of multiple cell types including the bone cells, adipocytes, endothelial cells, and nerve cells that all have crucial functions in the maintenance of bone homeostasis. Tumor cells severely disturb the tightly controlled cellular and molecular interactions in the bone marrow fueling their own survival and growth. While the role of bone resorbing osteo

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… Stromal cells of the tumor microenvironment, such as macrophages, express ARs and can be activated by neurotransmitters of the nervous system [ 103 ]. … Osteoblasts are “educated” by crosstalk with metastatic breast cancer cells in the bone tumor microenvironment Breast Cancer Res 2019 21 31 10.1186/s13058-019-1117-0 30813947 PMC6391840 36. Brown H.K. Ottewell P.D. Evans C.A. Holen I. …

Integrated in vivo and in vitro experiments with multi-omics analysis reveal SPP1 drives pancreatic cancer progression.

OBJECTIVE: To investigate the expression pattern of SPP1 in pancreatic cancer and its role in the tumor immune microenvironment, with functi … : SPP1 plays a critical role in regulating macrophage polarization and shaping an immunosuppressive tumor microenvironment in pancreatic cancer, suggesting its potential as a therapeutic target.

Microenvironmental arginine restriction sensitizes pancreatic cancers to polyunsaturated fatty acids by suppression of lipid synthesis.

Nutrient limitation is a characteristic feature of poorly perfused tumors. In contrast to well-perfused tissues, nutrient deficits in tumors impose metabolic constraints on cancer cells. The metabolic constraints created by the tumor microenvironment can lead to vulnerabilities in cancers. Identifying the metabolic constraints of the tumor microenvironment and the vulnerabilities that arise in cancers can provide new insight into tumor biology and identify promising anti-neoplastic targets. To identify how the microenvironment constrains the metabolism of pancreatic tumors, we challenged pancr…

Akt-Girdin signaling in cancer-associated fibroblasts contributes to tumor progression.

PI3K-Akt signaling is critical for the development, progression, and metastasis of malignant tumors, but its role in the tumor microenvironment has been relatively little studied. Here, we report that the Akt substrate Girdin, an actin-binding protein that regulates cell migration, is expressed and activated by Akt phosphorylation in cancer-associated fibroblasts (CAF) and blood vessels within the tumor microenvironment. Lewis lung tumors grafted into mice defective in Akt-mediated Girdin phosphorylation (SA transgenic mice) exhibited a decrease in both CAF infiltration and tumor growth, compa…

Endoplasmic Reticulum Stress: Triggers Microenvironmental Regulation and Drives Tumor Evolution.

BACKGROUND: The endoplasmic reticulum (ER) serves as a crucial hub for protein synthesis and processing, playing an essential role in mainta … giogenesis, cell migration, cell metabolism, and treatment resistance, and has a huge impact on the tumor microenvironment. MATERIALS AND METHODS: We conducted a literature review of scientific papers on the topic of ER stress in the tumor microenvironment. RESULTS AND DISCUSSION: This review focuses on the inducing factors of ER stress, the mechanism of the UPR signa …

Targeting Immunosuppressive Adenosine Signaling: A Review of Potential Immunotherapy Combination Strategies.

The tumor microenvironment regulates many aspects of cancer progression and anti-tumor immunity. Cancer cells employ a variety of immunosuppressive mechanisms to dampen immune cell function in the tumor microenvironment. While immunotherapies that target these mechanisms, such as immune checkpoint blockade, have had notable clinical success, resistance is common, and there is an urgent need to identify additional targets. Extracellular adenosine, a metabolite of ATP, is found at high levels in the tumor microenvironment and has potent immunosuppressive properties. Targeting members of the aden…