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CAN > L25: The Tumour Microenvironment > Flashcards

L25: The Tumour Microenvironment Flashcards

1
Q

What does the tumour micro-environment look like

A

It contains many non-malignant cells

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2
Q

What are the non malignant cells found in the micro-environment

A 
Cancer associated fibroblasts 
Pericytes 
Endothelial cells 
Myeloid cells 
Lymphocytes 
Extra-cellular matrix i.e collagen
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3
Q

What happens to the stromal cells as the tumour cells develop

A

Become abnormal

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4
Q

Is tumourigensis and stormagensis independent processes

A

Yet but occur at the same time i.e cancer cells promote priming of stroma and primed stroma support the tumour growth (like a cycle)

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5
Q

Does cancer have inflammation

A

Yes

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6
Q

What can reduce inflammation and therefore the risk of cancer

A

NSAID

Cox-2 inhibitors

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7
Q

In Hodgkin lymphoma what are the malignant cells surrounded by

A

Non tumour components

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8
Q

What does Hodgkin cells provide to the non tumour cells

A

Growth signals to non tumour cells so they can proliferate

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9
Q

What does non tumour cells provide to the Hodgkin cells

A

Growth signal to the Hodgkin cell so it survivors

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10
Q

Which cells in the tumour micro-environment are capable of killing the tumour

A

Cytotoxic T cell

Natural killer cells

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11
Q

What is the role of cytotoxic T cells

A

Recognise cancer antigens on the tumour cell and kill them

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12
Q

If there are immune cells that can kill tumours cell in the micro-environment why is there immunosupression

A

Due to the production of cytokine by the tumour cells so cytotoxic T cell and natural killer cells are overwhelmed by the number of cell that oppose their response

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13
Q

Which cell can prevent cytotoxic T cells from killing the tumour cell

A

T regulatory cells

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14
Q

How is the tumour micro environment recruited

A

Via 2 lipids called:
Lysophosphatidic acid
Sphingosine 1 phosphate

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15
Q

What does lysophosphatidic acid promote

A

Lymphocyte entry

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16
Q

What does sphingosine 1 phosphate promote

A

Lymphocyte retention

17
Q

Therefore what are patients with hodgkin lymphoma have less lymphocytes in the blood

A

They become retained in the tissue due to sphingosine 1 phosphate

18
Q

What other soluble factors does cancer cells produce

A

PDGF

19
Q

What is PDGF involved in

A

Differentiate fibroblast to myofibroblast
Recruit macrophages
Activate myofibroblast

20
Q

What are myofibroblasts

A

Altered forms of fibroblasts

21
Q

What does myofibroblast produce

A

Collagen and matrix proteins

22
Q

What are myofibroblast important for

A

Wound healing

23
Q

How do myofibroblast contribute to cancer cancer

A

Produce collagen and immunosupressive factors such as:
TGF beta
HGF- growth factor
VEGF- angiogenesis
MMPS- degrade basement membrane important for EMT i.e metastasis

24
Q

How does collagen promote tumour growth

A

1) There is expression of collagen receptor called discoidin domain receptor 1 (DDR1) which is an oncogene cell tyrosine kinase that binds to collagen
2) when collagen binds to DDR1 conformational change occurs
3) downstream signalling occurs for growth

25
Q

In cancer what are the 2 main macrophages

A

M1 macrophages

M2 macrophages

26
Q

What are M1 macrophages

A

Anti tumour activity that defect action bacteria and cause immunostimulation

27
Q

What are M2 macrophages involved in

A

Angiogensis and tissue remodelling for tumour promotion
Downregulate M1 macrophages
Associated with cancer

28
Q

What happens to fibroblast when they are acitvated in cancer

A

Become cancer associated fibroblast

29
Q

Give an example of a cancer associated fibroblast

A

Myofibroblast

30
Q

What other factors does cancer associated fibroblast produce that cause scarring

A

Extracellular matrix

31
Q

Why do many cancer cells how lymphoneia i.e low lymphocytes

A

Due to expression of sphingosine 1 phosphate that causes retention of the lymphocyte

CAN (25 decks)

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