Tumour Microenvironment Flashcards

1
Q

Define stromagenesis.

A
  • The development of a tumour microenvironment that supports malignancy.
  • It is the process by which the tumour microenvironment transitions from tumour-suppressive to tumour-permissive.
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2
Q

List 3 cancers that are associated with inflammatory conditions.

For cancer, give an example of a specific inflammatory condition with which the cancer is associated.

A

1 - Hepatitis and hepatocellular cancer.

2 - Helicobacter pylori gastritis and gastric cancer.

3 - Inflammatory bowel disease and colon cancer.

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3
Q

How can a tumour microenvironment support tumour growth?

A
  • The tumour microenvironment can support tumour growth by providing growth and survival signals to the tumour cells.
  • In turn, the tumour reciprocates by providing growth and survival signals to the tumour microenvironment in a positive feedback loop.
  • There are instances in which the tumour can destroy aspects of the microenvironment, e.g. immunosuppression by cytokine production.
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4
Q

Which cell predominates in the stroma of Hodgkin lymphoma?

Why is this advantageous for the tumour?

A
  • CD4+ Treg cells predominate in the stroma of Hodgkin lymphoma.
  • This is advantageous for the tumour as the Tregs dampen the immune response of cytotoxic T CD8+ cells against the tumour.
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5
Q

Give an example of a mechanism by which the tumour microenvironment is set up in Hodgkin lymphoma.

A
  • Lysophosphatidic acid is required for lymphocytes to enter a lymph node. It is overexpressed in Hodgkin lymphoma tumours, promoting excessive lymphocyte recruitment.
  • Sphingosine-1-phosphate is required for lymphocytes to exit a lymph node. However, it is overexpressed in Hodgkin lymphoma tumours as when it is overexpressed, it has the opposite effect (causes lymphocyte retention).
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6
Q

Why do tumours cause lymphopenia?

A

Tumours cause lymphopenia due to lymphocyte reruitment (and retention) to the tumour tissue, resulting in removal of lymphocytes from the blood.

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7
Q

What are myofibroblasts?

A
  • Myofibroblasts are an altered form of fibroblasts that have hybrid properties of both fibroblasts and smooth muscle cells.
  • They produce matrix proteins (e.g. collagens and MMPs) and can contract.
  • These properties make myofibroblasts important for normal wound healing.
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8
Q

What are cancer-associated fibroblasts?

Give an example of a cancer-associated fibroblast.

A
  • Cancer-associated fibroblasts are a group of fibroblasts that contribute to many aspects of tumour progression.
  • Myofibroblasts are an example of cancer-associated fibroblasts.
  • Their functions in cancer progression include recruiting inflammatory cells contributing to tumour invasion, promoting angiogenesis, etc.
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9
Q

Why is pancreatic adenocarcinoma relatively resistant to chemotherapy?

A
  • Pancreatic adenocarcinoma is relatively resistant to chemotherapy due to the abundance of cancer-associated fibroblasts in the tumour.
  • The fibroblasts produce high concentrations of collagen, which make it difficult for the chemotherapy drugs to diffuse across the tissue.
  • This is made worse by the poor vascularisation of pancreatic adenocarcinomas.
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10
Q

Give an example of collagen behaving as a signalling molecule.

A
  • Collagen is a ligand for many receptors, including DDR1, an oncogenic tyrosine kinase.
  • Mutated variants of DDR1 are implicated in various cancers, e.g. lung cancer.
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11
Q

How do macrophages contribute to tumour progression?

A
  • There are two types of macrophages: M1 and M2 macrophages.
  • M1 macrophages are involved in phagocytosis of pathogens and secrete cytotoxic molecules and cytokines that contribute to the immune response.
  • M2 macrophages dampen the immune response, and are recruited with Tregs. They are also involved in tissue remodeling and angiogenesis.
  • The two forms of macrophages are interchangeable.
  • Tumours produce signalling molecules that convert M1 macrophages into M2 macrophages.
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