lect 20 Flashcards
helibacter pylori
stomach cancer
Hep B and c viruses
liver cancer
HPV
cervival and head and neck cancer
what are cancer enabling characteristics
genome instabiity and tumor promoting inflamation
what are the 6 halmarks of cancer
sustaining proliferative signialling
evading growth supressors
resisting cell death
inducing angiogeneis
activating invasion and metastasis
enabling replicative immortality
what cancers do immunosupressed patients have
lymphomas
what ko gene is associated w carcinoma
IFN -/-
large infiltrating lymphocytes and cancer
improved survival esp for CD8+ and TH1 (IFNY TNFa)
antigens unique to tumors
tumor specific antigens
antigens derived from normal cellular proteins
tumor associated antigens
examples of TSA
point mutations
oncogene products like mutatnt ras proteins
mutant supressor P53
Mutant cell cycle regulator CDK5
what are TAA examples
prostate specific antigen
alpha fetal protein
carcinoembryonic antigen
alpha fetal protein cancer
liver cancer
carcinoembryonic antigen cancer
bowel cancer
cancer immunoediting concept
EEE
Elimination
Equilibrium
Escape
proposed that immune system supresses development of cancer
erlich
proposed immune surveilence theory - immune system recognizes and removes transformed cells before they become cancer
burnett and thomas
reported that freq of cancer in immune def mice is same as immune competent mice
stutman
how are transformed cells removed
by combination of innate and adaptive immune cells
how do NK cells kill transformed cells
produce cytokines like IL12 and IFNY
interact w ligands upregulated on tranformed cells
kill cells w altered MHCI expression
ADCC
cytokine TNFa
apoptosis
cytokines IFNY
activate macrophages
neo tumor antigens
antigens edited by tumor cells bc they are unstable genetically and want to avoid antigen specific T cells and the adaptive immune response
balance bc well make more ag specific T cells and tumor antiggens will continue to change
in vivo CAR
using viral vectors and nanoparticles to put CAR plasmid in there
- they target T cells w anti CD3 to put their CAR DNA or mRNA
risk of in vivo CAR
cytokine storm
generations of CAR
first generation can produce signal 1
second can produce signal 2
and third has costimulatory domains
transfer of cancer case
melanoma in equilibrium that wazs thought to be gone was transferred through a kidney transplant
melanoma transfer case patients 1 and 2
patient 1 died and patient 2 had IFNY treatment that cuased rejection of the kidney
what cytokines are in an antitumor microenvrioemnt
IFN Y and IL 12
what cytokines are in a protumor enviroment
TGF B
IL10
how do cancer cells escape immune ersonse
produce immunosupressive factors
produce T reg ccytokines
attract suppresor type macrophags
upregulate co inhibitory molecules- dampens anti tumor response
what are the escape mechanisms for tumors
HLA
-not inducing immune response: lack costimulation, upregulation of co inhibition, or down regulation of HLA
if they dont express MHC I ti wont be recognized by CD8+
but then NK cells kill them bc they dont have MHC I
other tumor escape mechanisms
upregulate PDL1 on tumor
fibrin and collagen- hiddne from immune system
secrete immunosupressive cytokines and factors- trigger immunosupressive macrophages or regulator T cells
T cells exhausted and upregulate coinhibitory receptors like CTLA4 and pD1
low immunogenicity antigen
coleys toxin
cancer immunotherapy treatment that has heat killed bacteria
waht is coleys toxin used for
bone and soft tissue sarcoma
activated immune system but not used today
non specific immunotherapy
IL2 for renal and cell carcinoma
adverse effects too high
what immmunotherapy cancer treatment is still uesd today
injection of BCG bacteria into bladder
attracts immune cells such as macrophages and DCand activates anti tumor immunity
list the cancer immunotherapy strategies
- toxin conjugatess mAB
- adoptively transferred ag loaded DC
- adoptively transferred T ecll
- engineered CAR T cell
- immune checkpoint inhibitors (PD1 and CTLA4)
current mAB therapy for cancer
tumor molecules- herceptin (anti- HER2) and ritixumab (anti CD20)
immune cell molecuels (ipitilulmab anti CTLA4
what cancer vaccines are in use
vaccines against oncogenic viruses (HPV)
DC vaccines
oncolytic viruses incorporating tumor antigens
what does CD20 do
induces apoptosis in B cells leads to tumor cell destruction
activates classical complement
cell lysis throuogh caspase 39
ADCC
phagocytosis through c3b complement
cancer vaccines using DC
take patient DCs and culture to express specific antigen and put back in patient and now DC can activate T cells in patient
