Tumour Microenvironment Flashcards
Define stromagenesis.
- 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.
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.
1 - Hepatitis and hepatocellular cancer.
2 - Helicobacter pylori gastritis and gastric cancer.
3 - Inflammatory bowel disease and colon cancer.
How can a tumour microenvironment support tumour growth?
- 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.
Which cell predominates in the stroma of Hodgkin lymphoma?
Why is this advantageous for the tumour?
- 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.
Give an example of a mechanism by which the tumour microenvironment is set up in Hodgkin lymphoma.
- 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).
Why do tumours cause lymphopenia?
Tumours cause lymphopenia due to lymphocyte reruitment (and retention) to the tumour tissue, resulting in removal of lymphocytes from the blood.
What are myofibroblasts?
- 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.
What are cancer-associated fibroblasts?
Give an example of a cancer-associated fibroblast.
- 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.
Why is pancreatic adenocarcinoma relatively resistant to chemotherapy?
- 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.
Give an example of collagen behaving as a signalling molecule.
- 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.
How do macrophages contribute to tumour progression?
- 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.
