Cancer (Lec 12) Flashcards
1
Q
Benign tumours
A
- encapsulated, localized
and limited in size - Non-cancerous
2
Q
Malignant tumours
A
- no size limit and invade
adjacent tissues - cancerous
3
Q
malignant transformation
A
Cells must gain multiple mutations in cell division,
proliferation and survival genes to become cancerous
can also be caused by:
- Mutagens = Chemical or Physical agents that increase mutation rate
- Carcinogens = Agents that increase risk of cancer
4
Q
Oncogenic viruses
A
- vruses that transform human cell
- associated with ~15% of
cancers
examples: - Hepatits B virus
- Epstein-Barr virus
- HIV-1
5
Q
7 Essential Characteristics of Cancer Cells
A
- They stimulate their own growth
- They ignore growth-inhibiting signals
- They avoid death by apoptosis
- They develop a blood supply: angiogenesis
- They leave their site of origin to invade other tissues: metastasis
- They replicate constantly to expand their numbers
- They evade and outrun the immune response
6
Q
Carcinomas
A
epithelial cell cancers
7
Q
Sarcomas
A
other cell type cancers
8
Q
Leukemias
A
circulating immune cell cancers
9
Q
Lymphomas
A
solid lymphoid cancers
10
Q
Myelomas
A
bone marrow cancers
11
Q
Metastasis
A
cancer cells form primary tumours escape/spread through the blood or lymphatics and form secondary tumours in new locations
12
Q
Tumour-antigens (neoantigens)
A
- Antigens unique to tumour cells and not present on normal cells
- peptide antigens presented by MHC class 1 on normal cells undergo mutation and become cancerous
- leads to presentation of mutant peptide from mutated cellular protein
13
Q
Tumour-associated antigens
A
- Antigens found on both tumour and normal cells, but overexpressed or abnormally expressed in cancer
- peptide antigens presented by MHC class 1 on normal cells undergo mutation and become cancerous
- can lead to reactivation of embryonic genes not normally expressed in differentiated cell
- or over expression of self protein that increases self-peptide presentation and recognition by T cells on tumour cells
14
Q
Immunosurveillance
A
stage in the progression of cancer where most mutated, malignant cells are eliminated
15
Q
Suppression of immune responses by cancer cells
A
- Cancer cells avoid T cells by
reducing MHC Class I but can be killed by NK cells - Immune system imposes
selection on tumour cells that have reduced expression of tumour antigens or mutations - Cancer cells also secrete cytokines to manipulate immune response to be anti-inflammatory/immunos ppressive
- MIC stress proteins can be cleaved from cell surface by proteases to prevent
cancer cells from NK cell mediated killing
16
Q
MIC and cancer cells
A
- tumour cells have increased MIC expression
- NK cells can bind MIC and kill tumour cells
- A variant tumour cell cleaves MIC from its cell surface
- soluble MIC then binds to lymphocytes
- variant tumour cell is not killed and survives to proliferate and cause cancer
17
Q
T cell exhaustion
A
- When tumours are detected and progressing, CD8 T cells can no longer keep up with cancer cells
- Caused by chronic inflammation and presence of antigen
- leads to cancer progression
18
Q
What are tumour mechanisms to avoid immune regulation?
A
- low immunogenicity
- tumour treated as self antigen
- antigenic modulation
- tumour-induced immune suppression
- tumour-induced privileged site
19
Q
Low immunogenicity
A
- tumour cells fail to adequately activate the immune system, making them “invisible”
- they have no peptide:MHC ligand
- no adhesion molecules
- no co-stimulatory molecules
20
Q
Tumour treated as self antigen
A
- immune system tolerates the tumour because it recognizes its antigens as “self”, leading to no strong immune activation
- tumour antigens taken up and presented by antigen presenting cells (APCs) in absence of co-stimulation tolerize T cells
21
Q
antigenic modulation
A
- tumour removes or downregulates that antigen from its surface
- T cells will not eliminate tumours that have lost immunogenic antigens
22
Q
tumour-induced immune suppression
A
- tumour cells manipulate the immune system to create a suppressive environment
- factors secreted by tumour cells inhibit T cells directly
23
Q
tumour-induced privileged site
A
factors secreted by tumour cells create a physical barrier to the immune system
24
Q
Cancer Immunotherapies: Antibodies
A
- Antibodies that recognize cell-surface antigens on tumours are increasing in
usage for cancer treatments, causes Antibody dependent cell cytotoxicity (ADCC) - tumour-specific antibody binds to the tumour cell
- NK cells with Fc receptors are activated to kill the tumour cells
25
Cancer Immunotherapy: Immunotoxin
- immunotoxins are a conjugate of a biological toxin and an antibody
- antibody component specifically targets cancer cells by recognizing and binding to tumour-associated antigens on their surface
- Once the antibody binds to the target cell, the toxic substance is delivered into the cell
- Targeted delivery of drug to tumour cells
26
Cancer Immunotherapy: Radioactive Antibody
- radioactive antibody binds to the malignant B cells and irradiates them
- radiation damages the cell's DNA and kills them
- Can help image tumours or kill the cells based on the
radioactive isotope
27
Cancer Immunotherapy: Antibodies Blocking
Inhibitory Receptors
- inhibitory receptors are molecules on T cells that downregulate immune responses
- Cancer cells exploit these checkpoints to suppress immune responses
- Blocking the inhibition of
T cell activation through
antagonistic antibodies prevents exploitation by cancer cells
28
Checkpoint inhibitor (cancer immunotherapy)
- class of drugs that block immune checkpoint proteins—molecules that normally keep immune responses in check
- By blocking these checkpoints, the inhibitors unleash T cells to recognize and destroy cancer cells
29
Adoptive Cell Transfer (Cancer immunotherapy)
involves collecting and modifying a patient’s immune cells, then reinfusing them to help fight cancer more effectively
30
Cyclophosphamide and Fludarabine in adoptive cell transfer
- Lymphocyte depleting agents used before adoptive cell transfer (ACT)
- they reduce the number of existing immune cells that might compete with or inhibit the infused therapeutic T cells
- create space in immune system for new T cells
31
CAR T Cell Therapy
- blood is collected to obtain T cells and T cells are separated and removed
- they are genetically altered to have special receptors called chimeric antigen receptors (CAR)
- millions of CAR T cells are grown
- chemo is given before this therapy
- then new CAR T-cells are introduced into the bloodstream
- Can cause severe side effects
32
Chimeric antigen receptors (CARs)
- Genetic engineering of T cell receptor to enhance
targeting towards tumour antigens
- No requirement for MHC presentation of peptides
as recognition domain on cell surface is from an
antibody
- Includes multiple signalling
domains, typically one for each signal required for T cell activation
- Increases T cell killing and reduces development of anergy
33
Protein-Specific Chimeric Antigen Receptors (CARs)
- genetically engineered receptors that allow T cells to recognize and bind to specific proteins (antigens) expressed on the surface of cancer cells
example:
CAR T cells recognizing a B
cell protein = killing of B
cell tumour
