Tumor Microenvironment Bone Marrow Chemotherapy

BACKGROUND: Platinum-drugs based chemotherapy in clinic increases the potency of tumor cells to produce M2 macrophages, thus leading to poor anti-metastatic activity and immunosuppression. Lysosome metabolism is critical for cancer cell migration and invasion, but how it promotes antitumor immunity in tumours and macrophages is poorly understood and the underlying mechanisms are elusive. The present study aimed to explore a synergistic strategy to dismantle the immunosuppressive microenvironment of tumours and metallodrugs discovery by using the herent metabolic plasticity...

Formyl peptide receptor-1 (FPR1) is a pattern recognition receptor that is mostly expressed by myeloid cells. In patients with colorectal cancer (CRC), a loss-of-function polymorphism (rs867228) in the gene coding for FPR1 has been associated with reduced responses to chemotherapy or chemoradiotherapy. Moreover, rs867228 is associated with accelerated esophageal and colorectal carcinogenesis. Here, we show that dendritic cells from Fpr1 -/- mice exhibit reduced migration in response to chemotherapy-treated CRC cells...

Chemoresistance is a significant problem in the effective treatment of bone metastasis. Adipocytes are a major stromal cell type in the bone marrow and may play a crucial role in developing microenvironment-driven chemoresistance. However, detailed investigation remains challenging due to the anatomical inaccessibility and intrinsic tissue complexity of the bone marrow microenvironment. In this study, we developed 2D and 3D in vitro models of bone marrow adipocytes to examine the mechanisms underlying adipocyte-induced chemoresistance...

Several diseases have been linked to the dysfunction of anoctamins. Anoctamins play a wide range of physiological roles, including cell proliferation, migration, epithelial secretion, and calcium-activated chloride channel activity. However, the function of anoctamin 10 (ANO10) in breast cancer is still unclear. ANO10 was highly expressed in bone marrow, blood, skin, adipose tissue, thyroid gland and salivary gland, while ANO10 was expressed at low levels in liver and skeletal muscle. Compared to benign breast lesions, the protein level of ANO10 was lower in malignant breast tumors...

Acute myeloid leukemia (AML) therapies have been significantly improved by the development of medicines that can target BCL-2. On the other hand, non-recurrent alterations in oncogenic pathways and gene expression patterns have already been linked to therapeutic resistance to venetoclax therapy. Bone marrow mesenchymal stromal cells (BM-MSCs) support leukemic cells in preventing chemotherapy-induced apoptosis by mitochondrial transfer in leukemic microenvironment. In this study, we investigated the enhancement of the antitumor effect of BCL-2 inhibitor venetoclax by dexamethasone...

In acute leukemia, the stromal microenvironment of the bone marrow that regulates hematopoiesis is modified under the influence of malignant cells. Chemotherapy also adversely affects stromal cells. Multipotent mesenchymal stromal cells (MSC) are involved in the formation of the stromal microenvironment and in the regulation of normal and tumor hematopoietic cells. The properties of MSC from the bone marrow of patients with acute myeloid and lymphoid leukemia were studied at the onset of the disease and after achieving remission...

BACKGROUND: The bone/bone marrow is one of the most common sites for metastatic solid tumors. Moreover, the tumor microenvironment is an essential part of cancer homeostasis. Previously, it was shown that cytochrome P450 enzymes (CYPs) are present in the bone marrow (BM) microenvironment, particularly in the mesenchymal stroma cells, at levels comparable to those of hepatocytes. It was found that the CYPs play important roles in nurturing and maintaining normal hematopoietic stem cells as well as multiple myeloma and leukemia cells, including protecting them from toxic insults...

Acute myeloid leukemia (AML) arises from the cells of myeloid lineage and is the most frequent leukemia type in adulthood accounting for about 80% of all cases. The most common treatment strategy for the treatment of AML includes chemotherapy, in rare cases radiotherapy and stem cell and bone marrow transplantation are considered. Immune checkpoint proteins involve in the negative regulation of immune cells, leading to an escape from immune surveillance, in turn, causing failure of tumor cell elimination. Immune checkpoint inhibitors (ICIs) target the negative regulation of the immune cells and support the immune system in terms of anti-tumor immunity...

OBJECTIVE: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder resulting from a complex interplay between leukemic cells and supporting factors from their microenvironment. In this context, extracellular vesicles (EVs) have been shown to play an essential role in forming a tumor-protective microenvironment. In this study, we examined the influence of AML-derived EVs on cellular and molecular characterization of bone marrow mesenchymal stromal cells (BM-MSCs), particularly alteration in the expression of genes (IL-6, Gas-6, and Galectin-3) relating to relapse and chemoresistance...

Conventional chemotherapy represents the main systemic treatment used for triple-negative breast cancer (TNBC) patients, although many of them develop drug resistance. The hypoxic TME is the crucial driver in the onset of insensitivity to chemotherapy. In this research, we elucidated the role played by bone marrow-derived mesenchymal stem cells (BM-MSCs) in reducing cisplatin effects in TNBC. BT-549 and MDA-MB-231 cells, grown under hypoxic conditions in the presence of conditioned medium obtained from BM-MSCs (CM-MSCs), showed a strong cisplatin insensitivity and increased expression levels of carbonic anhydrase IX (CA IX)...

The receptor tyrosine kinase AXL is an emerging driver of cancer recurrence, while its molecular mechanism remains unclear. In this study we investigated how AXL regulated the disease progression and poor prognosis in non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC). We performed AXL transcriptome analysis from TCGA datasets, and found that AXL expression was significantly elevated in NSCLC and TNBC correlating with poor prognosis, epithelial-mesenchymal transition (EMT) and immune-tolerant tumor microenvironment (TME)...

Pancreatic cancer has the highest mortality rate of all major cancers, with a 5-year survival rate of about 10%. Early warning signs and symptoms of pancreatic cancer are vague or nonexistent, and most patients are diagnosed in Stage IV, when surgery is not an option for about 80%-85% of patients. For patients with inoperable pancreatic cancer, current conventional treatment modalities such as chemotherapy and radiotherapy (RT) have suboptimal efficacy. Tumor progression is closely associated with the tumor microenvironment, which includes peripheral blood vessels, bone marrow-derived inflammatory cells, fibroblasts, immune cells, signaling molecules, and extracellular matrix...

Bone metastatic breast cancer has severely threatened the survival and life quality of patients. Due to the suboptimal efficacy of anti-metastatic chemotherapeutic drugs and the complicated bone marrow microenvironments, effective treatment of metastatic breast cancer remains challenging for traditional clinical approaches. In this work, we developed a mesoporous nanoplatform (m-CuS-PEG) with the co-loading of CuS nanodots and a chemotherapeutic drug cisplatin for the combined photothermal-chemotherapy of bone-metastasized breast cancer...

Malignant tumors, one of the worst-case scenarios within human health problems, are now posing an increasing threat to the well-being of the global population. At present, the treatment of malignant tumors mainly includes surgery, radiotherapy, chemotherapy, immunotherapy, etc. Radiotherapy and chemotherapy are often applied to inoperable tumors, and some other tumors after surgery as important adjuvant therapies. Nonetheless, both radiotherapy and chemotherapy have a series of side effects, such as radiation-induced lung injury, and chemotherapy-induced bone marrow suppression...

Both the tumor and tumor microenvironment (TME) are crucial for pathogenesis and chemotherapy resistance in multiple myeloma (MM). Bortezomib, commonly used for MM treatment, works on both MM and TME cells, but innate and acquired resistance easily develop. By single-cell RNA sequencing (scRNA-seq), we investigated bone marrow aspirates of 18 treatment-naïve MM patients who later received bortezomib-based treatments. Twelve plasma and TME cell types and their subsets were identified. Suboptimal responders (SORs) to bortezomib exhibited higher copy number alteration burdens than optimal responders (ORs)...

BACKGROUND: Waldenstrom Macroglobulinemia (WM) is a rare and indolent lymphoma of B-cell origin characterized by elevated monoclonal IgM, with MYD88L265P mutation and CXCR4 mutation as common molecular alterations. B-cell Acute Lymphoblastic Leukemia (B-ALL) is clinically heterogeneous, characterized by abnormal proliferation and aggregation of immature lymphocytes in the bone marrow and lymphoid tissue. WM and ALL are hematologic malignancies of B-cell origin with completely different clinical manifestations and biological features...

AIMS: There is emerging evidence that antineoplastic agents and the cytotoxic effects on tumor tissues attenuate the benefits of chemotherapy due to tumor microenvironment changes. Nevertheless, the actual relationship between chemotherapy and recurrent tumors in which the genotypes differ from the original tumor after chemotherapy is unclear. MATERIALS AND METHODS: Bone marrow transplantation, flow cytometer, immune inhibition and immunofluorescence will be utilized to investigate the effect of antineoplastic agents on bone-marrow-derived cells (BMDCs) release and recruitment, and to explore the pathways and mechanisms of antineoplastic agents in promoting tumor growth...

Acute myeloid leukemia (AML) is a highly heterogeneous malignancy of the blood and bone marrow, characterized by clonal expansion of myeloid stem and progenitor cells and rapid disease progression. Chemotherapy has been the first-line treatment for AML for more than 30 years. Application of recent high-throughput next-generation sequencing technologies has revealed significant molecular heterogeneity to AML, which in turn has motivated efforts to develop new, targeted therapies. However, due to the high complexity of this disease, including multiple driver mutations and the coexistence of multiple competing tumorigenic clones, the successful incorporation of these new agents into clinical practice remains challenging...

BACKGROUND: Colorectal cancer (CRC) has a high mortality rate and can develop in either colitis-dependent (colitis-associated (CA)-CRC) or colitis-independent (sporadic (s)CRC) manner. There has been a significant debate about whether mast cells (MCs) promote or inhibit the development of CRC. Herein we investigated MC activity throughout the multistepped development of CRC in both human patients and animal models. METHODS: We analyzed human patient matched samples of healthy colon vs CRC tissue alongside conducting a The Cancer Genome Atlas-based immunogenomic analysis and multiple experiments employing genetically engineered mouse (GEM) models...

Multiple myeloma (MM) remains an incurable, genetically heterogeneous disease characterized by the uncontrolled proliferation of transformed plasma cells nurtured within a permissive bone marrow (BM) microenvironment. Current therapies leverage the unique biology of MM cells and target the immune microenvironment that drives tumor growth and facilitates immune evasion. Proteasome inhibitors and immunomodulatory drugs were initially introduced to complement and have now supplanted cytotoxic chemotherapy as frontline anti-myeloma agents...