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Cancer > Tumour immunology > Flashcards

Tumour immunology Flashcards

1
Q

How can tumours evade immune surveillence?

A
  1. They’re not immunogenic
  2. They arise from self cells
  4. Tumour cells can suppress immune function- TGFbeta
  5. Factors secreted by tumour cells can create a physical barrier
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2
Q

What is the innate immune system, and which cells are associated with it?

A

This type of defence is innate/ you’re born with it- its action does not depend on previous exposure to a pathogen
Cells: neutrophils, macrophages, natural killer cells

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3
Q

What is the adaptive immune system, and which cells are associate with it?

A

Slower more variable response, selective and specific to the pathogen
Cells: professional antigen presenting cells, B cells, T cells

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4
Q

What cell is predominant in the tumour microenvironment?

A

Macrophages

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5
Q

How can macrophages lead to tumour progression?

A

Factors secreted by macrophages:
TNFalpha and IL-6= enhance tumour cell growth
TGFbeta= enhances tumour cell tissue invasion
TNFalpha, IL-6 and TGFbeta= affect stromal cells and enhance metastasis

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6
Q

How can macrophages suppress tumour growth?

A

Factors secreted by macrophages:
IL-12= stimulates natural killer cells and cytotoxic t lymphocytes
Tumour growth is suppressed

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7
Q

Where are macrophages derived from?

A

Embryonic source, but more importantly- the bone marrow

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8
Q

What are TAMs?

A

Tumour-associated macrophages
found at tumour sites
chemotherapy can stimulate the production of tams
in breast cancer- 50-80% of the tumour can be TAMs

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9
Q

What are the types of TAMs?

A 
M1= immunostimulatory 
pro-inflammatory 
tumoricidal 
perform ADCC (antibody dependent cellular cytotoxicity) 
are scarce
M2= immunosupressive 
pro-angiogenic 
maintain t-regs 
do not perform ADCC
predominant type of TAM
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10
Q

What was a recent discovery in immunotherapy history?

A

2015- oncolytic virus treatment

viruses can replicate in cancer cells but not in normal cells

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11
Q

What are the 5 main types of immunotherapy?

A
  1. Monoclonal antibodies
  2. Immune checkpoint inhibitors
  3. Cancer vaccines
  4. Adoptive cell transfer
  5. Cytokines
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12
Q

What is active immunotherapy?

A

Helps your host immunity becomes responsive to tumours

involves vaccination

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13
Q

What is passive immunotherapy?

A

The transfer of t. cells or antibody therapies

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14
Q

What are thy types of cancer vaccine?

A
  1. Killed tumour vaccine
  2. Purified tumour antigens
  3. Professional APC based vaccine
  4. Cytokine and costimulatory enhanced vaccines
  5. DNA vaccines
  6. Viral vectors
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15
Q

What is cell-based immunotherapy?

A

Therapy based on activating patients own immune system to attack cancer
cells used in this therapy: dendritic cells, t. cells and monocytes

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16
Q

Where are dendritic cells found, and what do they do?

A

Found under the epidermis- langerhan cells

the cells detect and engulf foreign invader cells and present a piece of the invader on their surface

17
Q

How to make a dendritic cell vaccine?

A

Isolate white blood cells
enrich them to increase their population
lots of things activate a DC cell

18
Q

What happens in T cell therapy?

A 
Take a tumour biopsy
cut the tumour into small pieces
isolate T cells
expand them in the lab
put the T cells back into the patient
T cells=  killer cells
19
Q

Why aren’t natural killer cells or stem cells as good as dendritic cells or T cells in therapy?

A

Cant expand them as well

Harder to isolate

20
Q

What form of therapy is TIL?

A

Form of adoptive cell transfer - cells are grown and expanded from resected metastatic tumour deposits

21
Q

What was the trojan horse treatment? What was the reason for it?

A

Trojan horse= macrophage
inside= cancer killing virus
Identified that hypoxic areas in tumour are a big issue- theyve changed their metabolism so they can starve but stay alive- are often resistant to chemotherapy and thus repopulate the tumour
TAMs accumulate in areas of hypoxia- if we can use TAMS as a vehicle- can reach the hypoxic areas

22
Q

How does the trojan horse treatment work?

A

Take blood from patient
isolate monocytes (which readily turn into macrophages)
infect the monocytes with the virus
put the macrophages back into the patient

23
Q

What are the problems associated with hypoxia?

A

Stimulates angiogenesis
suppresses the immune system
resistant to radio- and chemo-therapy

24
Q

What was the initial experiment using the trojan horse technique- what happened?

A

Nude mice (with no adaptive immune system) were implanted with prostate tumour cells
they were then injected with the macrophage therapy
48 hours later- the prostate was removed and the tumour was analysed
By using prostate-specific GFP reporter- visualised the macrophages
Saw that out of the 3 million injected- only a small proportion reached the tumour

25
Q

What was the result of combining the trojan horse treatment and chemotherapy (DOX)?

A

Shrank the tumours and kept them small

26
Q

What needs to happen next for this treatment?

A

Move to clinical trials- be used on prostate cancer patients
expand the approach to look at other tumour types
improve the delivery of the therapy to tumours- currently- can only use this therapy for tumours you can reach

27
Q

What is magnetic macrophage therapy?

A 
Removing monocytes from a patient
insert therapeutic virus 
load with ion particles 
put back the macrophages
the macrophages will circulate in the blood, but by using a magnetic field, can be moved to the location of the tumour
28
Q

How did magnetic macrophage therapy work with the trojan horse treatment?

A

Increased the traffic of macrophages to the tumour from 4% to 15%

29
Q

What is MRT?

A

Magnetic resonance targeting
Used the magnetic field inherent to MRI to steer magnetised macrophages to the target site
MRI- locates the tumour, but then uses magnetic field (in pulses of 30mins/1 hour) to steer the macrophages
can increase the amount of macrophages reaching the tumour to 50%

Cancer (16 decks)

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