class 4 yana Flashcards
Describe the metastatic cascade in cancer progression.
The metastatic cascade involves tumour cells escaping the primary site, invading surrounding tissue, intravasating into blood or lymphatic vessels, circulating, extravasating at a distant site, and forming a metastatic tumour.
How do immune cells like CD8+ T cells and NK cells restrict the metastatic outgrowth of cancer cells?
They recognize and restrict the growth of mutant and potentially immunogenic tumour cells during the metastatic cascade.
Define pre-metastatic niche in the context of cancer metastasis.
It refers to the environment of the future metastatic site, which is remotely prepared by tumour cells at the primary site.
What role do myeloid cells, particularly macrophages, play in the metastatic process?
They actively participate in metastatic processes and facilitate the escape of circulating metastatic cells from immune detection.
Describe the systemic enhancements of metastasis driven by primary tumours.
They involve myeloid cells that prepare distant sites to become pre-metastatic niches, thereby enhancing metastatic efficiency and altering haematopoiesis in the bone marrow.
Describe the role of chemokines and cytokines in the recruitment of immune cells in the primary tumour.
Chemokines and cytokines are secreted by cancer cells to recruit tumour-associated macrophages (TAMs), tumour-associated neutrophils (TANs), myeloid-derived suppressor cells (MDSCs), and regulatory T (TReg) cells, which directly suppress the cytotoxic functions of natural killer (NK) cells and CD8+ T cells.
What are the systemic factors produced by the primary tumour, and how do they contribute to the metastatic process?
The primary tumour produces systemic factors such as vascular endothelial growth factor A (VEGFA), TGFβ, tumour necrosis factor (TNF), and lysyl oxidase (LOX), which induce chemotactic protein expression and extracellular matrix remodelling in the metastatic sites before tumour cell arrival.
Define the function of immature myeloid cells in the pre-metastatic niche.
Immature myeloid cells are recruited to the pre-metastatic niche and form clusters, secreting matrix metalloproteinase 9 (MMP9) to promote the subsequent outgrowth of metastasizing cancer cells.
How do TAMs and TReg cells contribute to future metastasis in the pre-metastatic niche?
TAMs and TReg cells are recruited to the pre-metastatic niche by primary tumour-derived fibrin clots, CCL2, and CCL22, and these cells promote future metastasis.
Describe tumour-associated macrophages (TAMs and their marker profile.
TAMs are a distinct population of macrophages in the tumour microenvironment that promote tumour development and progression. They can be identified by markers such as CD11b, CD14, CD23, CD68, CD163, CD204, and others.
What are myeloid-derived suppressor cells (MDSCs) and how are they subdivided?
MDSCs are a heterogeneous population of myeloid cells increased in cancer patients. They are subdivided into monocytic and granulocytic MDSCs.
Define plasmacytoid dendritic cells (pDCs) and their characteristics.
pDCs are a small population of dendritic cells that link innate and adaptive immune responses. They have pro-inflammatory properties and immunosuppressive effects, characterized by expression of B220, CD11c, Siglec-H, PDCA1, and GR1.
Explain osteoclastogenesis.
Osteoclastogenesis is the process where haematopoietic stem cells differentiate into multinucleated osteoclasts with bone-resorbing activity.
How do cancer-associated fibroblasts contribute to the immunosuppressive function of immature myeloid cells?
They secrete granulocyte colony-stimulating factor (G-CSF), which promotes the immunosuppressive function of immature myeloid cells.
Describe metastasis-associated macrophages (MAMs) and their role in tumour progression.
MAMs are a distinct subset of tumour-associated macrophages recruited to metastatic sites, promoting tumour cell dissemination and outgrowth. They originate from inflammatory monocytes and are characterized by specific marker profiles.
How do myeloid progenitor cells contribute to the establishment of the pre-metastatic niche?
Myeloid progenitor cells are the central cell population that establishes the pre-metastatic niche. They are recruited by primary tumour-derived factors and can rapidly differentiate into metastasis-associated macrophages (MAMs) at pre-metastatic sites, enhancing tumour cell extravasation and survival.
Define tumour cell egress and explain the role of myeloid cells in this process.
Tumour cell egress refers to the migration of tumour cells from the primary site through the stroma and intravasation into blood vessels. Myeloid cells, such as TAMs and TANs, contribute to these early steps of metastasis by promoting tumour intravasation.
Describe the contribution of macrophages to tumour progression and metastasis.
Ablation of macrophages impairs the onset of angiogenesis and suppresses lung metastases, indicating their significant contribution to tumour progression and metastasis.
How do CD4+ T cells contribute to the process of tumour cell egress?
CD4+ T cells contribute to tumour cell egress through the modulation of macrophage phenotypes, although direct involvement of lymphocytes in tumour cell egress has not been reported.
Describe the role of histidine-rich glycoprotein in cancer cells.
Histidine-rich glycoprotein in cancer cells skews TAM polarization from a pro-tumorigenic to a tumour-inhibiting phenotype by downregulating placental growth factor (PGF) expression, which normalizes the leaky blood vessels and inhibits metastasis.
What is the function of TAMs in the tumor microenvironment?
TAMs (tumor-associated macrophages) are polarized from a tumour-reactive to a tumour-promoting state, contributing to the pro-metastatic function of TAMs.
Define the process of TAM polarization in the tumor microenvironment.
The tumor microenvironment polarizes recruited macrophages from a tumour-reactive to a tumour-promoting state, which can be suppressed by targeting signaling pathways that regulate TAM polarization.
How does the interaction between cancer cells and TAMs contribute to tumor metastasis?
The interaction between cancer cells and TAMs leads to the promotion of the first step of metastasis, including tumour angiogenesis, invasion, and intravasation, ultimately facilitating haematogenous dissemination of cancer cells.
