Tumour Immunology

Question 1

What is the word for cancer derived from?

Answer 1

latin word for “crab” referring to the ability of hte organism to hold on and not let go

Question 2

What are the causative agents of cancer?

Answer 2

viruses; chemical carinogens; spontaneous; UV and ionising radiation

Question 3

What does the uncontrolled cell growth in cancer result from?

Answer 3

abnormally high expression of genes that induce cell proliferation; defective expression of genes that normally control proliferation

Question 4

How is the induction of cancer by chemical carcinogens and UV/ionising radiation used experimentally?

Answer 4

in order to induce cancers in animal models

Question 5

Give examples of DNA viruses that cause cancer?

Answer 5

HPV; hepB; EBV; HTLV1

Question 6

What is the difference between cancer cells and normal cells?

Answer 6

clonal in origin; deregulated growth and lifespan; altered tissue affinity; resistance to apoptosis; change in surface phenotype and markers; tumour associated antigens

Question 7

What is the evidence for immune control of tumours?

Answer 7

animal models showed that pre-treatment of mice with killed tumour material could protect against a subsequent challenge with viable cells of same tumours- vaccine, T cell deficient mice were not able to do this, T cells transferred from the immunised mouse could protect a naive mouse

Question 8

Give example of normal testicular proteins that are expressed by melanoma and breast cancers?

Answer 8

MAGE-1 and MAGE-3

Question 9

What is the benefit of having a cancer with lots of mutations?

Answer 9

increased chance of expressing neoantigens and therefore an ability to activate the immune system

Question 10

What are the strategies of low immunogenicity that tumours use to escape the immune system?

Answer 10

downregulation or complete loss of MHC-I molecules; downregulation of molecules involved in antigen processing; overexpression of inhibitors of granzyme B and perforin pathway to prevent lysis

Question 11

What moelcules involved in antigen processing are downregulated by tumours?

Answer 11

TAP1; LMP2; tapasin- tapasin is progressively lost in colorectal carcinoma

Question 12

Give examples of cancers which downregulate MHC-I?

Answer 12

epithelial-cell cacners and melanomas

Question 13

How does the tumour become treated as a self antigen?

Answer 13

some tumour cells don’t express any abnormal antigen so immune system isn’t able to identify them; others express antigenic peptide to T cells in the absence of costimulation thereby resulting in tolerisation

Question 14

How do tumours induce immunosuppression?

Answer 14

encouragement of Treg development; IL-4;IL10 secretion to polarisae T cell responses; aberrant STAT3 actviation causes IL-6R receptor signalling to favour unrestrained grwoth; overexpression of TGFb; upregulation og PD-L1

Question 15

How do tumours create priviledged sites?

Answer 15

avoid detection by creating a physical barrier made of secreted collagen or fibrin which prevents cells penetrating the barrier and remaining ignorant

Question 16

How do tumours evade apoptosis?

Answer 16

abnormal regulation of Bcl2 family e.g Bcl-XL which are endogenous inhibitors of the mitochondrial death pathway

Question 17

How do tumours have unending replicative ability?

Answer 17

upregulate growth receptors; expression of telomerase; have activating mutation in cell-cycle regulator genes; mutations in p53 preventing its role in DNA repair and cell cycle arrest

Question 18

Who first noticed a relationship between immune activation and cancer regression?

Answer 18

Coley in the 1890s noticed a patients whose cancer regressed after severe skin infection so treated patients with some types of bacteria–Coley’s toxins

Question 19

What are the tumour specific antigens the reuslt of?

Answer 19

point mutations or gene rearrangement or viral antigens

Question 20

What are tumour associated antigens?

Answer 20

overexpressed antigens on tumour cells (also found no normal cells); developmental antigens which become derepessed; differentitation antigens

Question 21

What are the types of immunotherapy?

Answer 21

passive immunotherapy using antibodies; adoptive cell therapy; active-specific immunotherapy using vaccines; non-specific e.g cytokines

Question 22

what is bevacizumab?

Answer 22

anti-VEGF used in advanced colorectal cacner

Question 23

What are the limitations of passive immunotherapy?

Answer 23

clearance by soluble antigens; antigenic variation of the tumour (heterogeneity); inefficient killing/penetration into the tumour mass

Question 24

How is adoptive T cell therapy done?

Answer 24

excise tumour and culture TILs with IL-2 and test for high levels of IFNy production after stimulation and then clonally expand them and transfer them back in- melanoma; generate tumour specific TCR or CARs

Question 25

What did a phase I clinical trial with both anti-CTLA4 and anti-PD1 demonstrate?

Answer 25

tumour regression in around 50% of advanced melanoma, most with tumour regression of 80% or more

Question 26

Why is checkpoint blockade very successful in melanoma?

Answer 26

very immunogenic tumour

Question 27

How may checkpoint blockade be improved?

Answer 27

induce tumour cell destruction then block- increased immunogenicity; identify potential neoantigens and create vaccine and give with adjuvant and blockade; or give with specific T cells