Lecture 20 - Immunity to Cancer Flashcards
What is the elimination phase of cancer surveillance?
immune cells (NK, CD4, CD8, etc) recognize tumor cells and kill them before proliferation
What is the equilibrium phase of cancer surveillance?
no true tumor development but mutations arise which decrease immune cell effectiveness
What is the escape phase of cancer surveillance?
Rapid proliferation of tumor cells
What are the 7 steps to the cancer-immunity cycle
- cancer cell antigen release
- antigen presentation
- APC/T cell priming and activation
- T cell homing to tumors
- Infiltration of T cells into tumors
- recognition of tumor
- killing of cancer cells
What cell kills tumor cells
CD8+ (cytotoxic) T cells
What is the action of perforin?
aids in delivering contents of granules into the cytoplasm
What is the action of granzymes?
proteases which activate apoptosis
What is the action of granulysin?
antimicrobial that promotes apoptosis
What are the mechanisms by which tumors avoid immune recognition?
- low immunogenicity
- self antigen
- antigenic modulation
- tumor induced immune suppression
- tumor induced privileged site
How does a tumor evade the immune system by:
low immunogenicity
no adhesion, co-stimulatory molecules, MHC molecules present
How does a tumor evade the immune system by:
self-antigen treatment
tumor antigens taken up and presented by APCs tolerize T cells
How does a tumor evade the immune system by:
antigenic modulation
tumors will not present immunogenic antigens
How does a tumor evade the immune system by:
tumor-induced immune suppression
factors secreted by tumor cell inhibit t cells directly (IL-10, TGF-b, PDL-1)
How does a tumor evade the immune system by:
tumor induced privileged sites
tumor cells secrete factors that create a cell barrier
What two steps of the cancer immunity cycle is PDL 1 involved in
activation of APC/T cells
killing of cancer cells
What are the 5 types of cancer immunotherapies
- cell-based immunotherapy
- immunomodulators
- vaccines
- oncolytic viruses
- antibody based targeted therapies
Explain oncolytic virus immunotherapy
inside a healthy cell, virus does not replicate but it does within a cancer cell. when the cancer cell lyses antigens are presented to T cells by DCs - now T cells are “programmed” to kill cancer cells
T/F: CAR-T cell therapy is personalized medicine
TRUE
Explain CAR-T cell therapy
T cells are harvested from tumor patient, a retrovirus infects T cells with CD3/CD28, infected cells express anti-CD19, T cells are infused into patient and mediate antitumor activity
What do co-inhibitory receptors do
regulate uncontrolled activation of lymphocytes through competing with CD28 molecules
What are the two immune checkpoints
CTLA4 and PD1
What is ITIM and what is its job
Immunoreceptor Tyrosine-based Inhibitory Motif
recruits phosphatase
PDL-1 ____ T cell response
inhibits
What do blocking of antibodies on PD-1 or PDL-1 prevent
inhibition of T cells
