MSI Cancer Immunology

Question 1

Hallmarks of cancer include:
Sustaining proliferative signalling
Evading growth suppressors
Activating invasion and metastasis
Enabling replicative \_\_\_\_\_\_\_\_\_\_
Inducing angiogenesis
Resisting cell death

Answer 1

immortality

Question 2

The development of _______ of self-antigens can result in shielding of tumours from the immune system

Answer 2

tolerance

Question 3

The two most important cells that illicit and anti-tumour effect are the ____ cells (which kills cancer cells by secreting perforin and granzymes?) followed by the ___ cells which multiply and signal other parts of the immune system to come to the site of disease via cytokines. This leads to cell death by recruitment of further NK cells and T cells

Answer 3

NK cells, T cells

Question 4

The appearance of _____ Tumour infiltrating lymphocytes (TILs) in tumour, blood or lymph nodes usually suggests good prognosis in humans

Answer 4

CD8

Question 5

The presence of _____ cells in tumours is a predictor of reduced survival

Answer 5

Treg

Question 6

Higher incidence of cancer after immunosuppression, in immunodeficiency (AIDS) and _______

Answer 6

aging

Question 7

Patients with SCID have _____ deficiency, which subsequently lead to tumour development (in mouse studies)

Answer 7

Rag

Question 8

** Introduction of ___ (which is very immunogenic) into the bladder activates the immune system and results in targeting and killing of the cancer cells, with little effect on healthy cells

Answer 8

BCG

Question 9

2 types of tumour antigens have been identified on tumour cells:

Answer 9

Tumour-associated antigens (TAAs)

Tumour-specific antigens (TSAs)

Question 10

NOT unique to tumour cells and may be proteins that are expressed during foetal development

antigens normally expressed only at certain stages of differentiation

may also be proteins that are expressed only at very low levels on normal cells, but overexpressed in particular tumours

describes which type of tumor antigen?

Answer 10

Tumour-associated transplantation antigens (TATAs)

OR Tumour-associated antigens (TAAs)

Question 11

Unique to tumour cells and are not present on normal body cells

antigens encoded by genes specifically expressed by tumours (example is a p53 mutation)

antigens encoded by variant forms of mutated genes

describes which type of tumor antigen?

Answer 11

Tumour-specific transplantation antigens (TSTAs)

OR Tumour-specific antigens (TSAs)

Question 12

Tumour-associated transplantation Ag- mutation generates new peptide in class I MHC molecule. Also known as

Answer 12

neoantigens

Question 13

Overexpression of a normal protein represents which time of tumor antigen?

Answer 13

Tumour-associated transplantation antigens (TATAs)

Question 14

Inappropriate expression of embryonic gene represents what type of tumour antigen?

Answer 14

Tumour-associated transplantation antigens (TATAs)

Question 15

If a mutation generates a new peptide in class I MHC molecule, this represents what type of tumour antigen?

Answer 15

Tumour-specific transplantation antigens (TSTAs) (also known as neoantigens)

Question 16

Know that there are different types of tumour antigens that have potential consequences for cancer therapies:

Answer 16

Tissue differentiation Ags (TAA),
tumour germline “tumour-testis” Ags (TAA),
normal proteins overexpressed by cancer cells (TAA), Viral proteins (TSA),
or tumour-mutated Ags (TSA)

Question 17

Note that tumour germline antigens are not recognized in the ________, as those cells do not express Class I MHC.

Answer 17

testis

Question 18

Examples of tumour-specific mutated antigens (only expressed in tumour cells as a result of mutation):

Answer 18

Ras, p53

Question 19

Innate responses to tumours(not MHC restricted):
_________ cells
Can kill directly tumour cells, helped by interferon-alpha and -beta and IL-2
Macrophages
Can infiltrate tumour masses; known as tumour-associated macrophages (TAMs). Can be pro-
tumourigenic or anti-tumourigenic.

Answer 19

Natural killer (NK)

Question 20

Adaptive responses to tumours (T cell responses are MHC restricted)
________ T-cells
Can directly kill tumour cells via tumour antigen recognition
T helper cells
Produce a variety of cytokines that activate other types of immune cell
e.g. Interferon-gamma & TNF (macrophages); IL-2 (CD8+ T cells and NK cells)
B cells
Production of tumour-specific antibodies (may be functional or not)

Answer 20

Cytotoxic

Question 21

CD8 T cell activated by specific antigen presented by APC plus co-stimulation via ______/CD86 molecules

Activation results in production of IL-2 which drives proliferation

Answer 21

CD80

Question 22

In-built mechanisms of control of T cell responses:
Inhibitory receptors expressed by T cells – these interfere with co-stimulatory signalling

Examples are:
CTLA-4 (during activation): ligand is ___ molecules
PD-1 (during effector function): ligand is PD-L1
FAS: ligand is FASL

Answer 22

B7

Question 23

CTLA-4 binds B7 more avidly than does CD28 and delivers __________ signals to activated T cells

Answer 23

inhibitory

Question 24

A tumour mass consists of:
a heterogeneous population of cancer cells with varying degrees of mutation
a variety of resident and infiltrating host cells
secreted factors and extracellular matrix proteins
This is collectively known as the

Answer 24

tumour microenvironment.

Question 25

The tumour micro-environment refers to the normal cells, molecules, and ___________that surround and feed tumour cells.

Answer 25

blood vessels

Question 26

Factors such as TGF-beta, PD-L1 secreted by tumour cells can _____ T cells directly

Answer 26

inhibit

Question 27

Cytotoxic T cells refer to CD8+ T cells that have been activated via recognition of specific antigen presented on MHC ________ – also known as CTLs.

Answer 27

Class I

Question 28

The immune system can recognize cancer cells Most relevant immune responses mediated by NK cells and ______ T cells Recognition by immune cells can occur via altered cell surface molecules or via tumour antigens

Answer 28

cytotoxic

Question 29

the immune system's ability to recognize and destroy emerging cancer cells

Answer 29

Cancer immunosurveillance

Question 30

Theory that describes how the immune system can kill cancer cells; but can also induce changes in the tumour resulting in tumour cell escape and further growth of tumour mass (by epigenetic changes or Darwinian selection)

Answer 30

Cancer immunoediting theory

Question 31

What are the "3 E's" of cancer immunoediting?

Answer 31

Elimination, equilibrium, escape

Question 32

One way that tumour cells "escape" from T cell recognition is via loss of _______

Answer 32

MHC I

Question 33

Some tumour cells develop into cells that express very low (or none) levels of MHC Class I and these cells are not recognized by cytotoxic T cells so can survive and proliferate = _______ phase

Answer 33

Escape

Question 34

Some tumour cells develop into cells that express only moderate levels of MHC Class I and so survive for longer than those expressing higher levels, but are eventually killed by cytotoxic T cells (4). As these moderately MHC expressing cells survive longer before being killed, they have longer to proliferate and so generate new cancer cells before eventually being killed = ___________ phase of the 3Es model where the tumour mass is in dynamic equilibrium with the immune system.

Answer 34

Equilibrium

Question 35

The tumour cells express MHC Class I on their surface at normal levels and present tumour antigens via these MHC molecules which are recognised by cytotoxic T cells. Some of the tumour cells develop into cells expressing higher levels of MCH Class I molecules and so are recognised and killed by cytotoxic T cells faster than other cells in the tumour. This killing of these tumour cells may reduce the size of the tumour mass = ____________ phase of the 3Es model.

Answer 35

Elimination

Question 36

** Mechanisms of tumour escape: Reduced levels or absence of MHC I molecules on tumour so that they can not be recognized by cytotoxic T cells Some tumours stop expressing the antigens recognized by immune system These tumours are called “_____ ______ ______” Production of immunosuppressive factors by tumor e.g. transforming growth factor (TGF-β), PD-1 ligand (PD-L1)

Answer 36

antigen loss variants

Question 37

Tumour evasion mechanisms of the immune system: Low immunogenicity (Low/absent MHC 1): No peptide: MHC ligand, no adhesion molecules, no co-stimulatory molecules Antigenic __________ (Ag-loss variants)- Ab against tumour cell-surface Ags can induce endocytosis and degradation of the Ag. Immune selection of Ag-loss variants. Tumour-induced immune suppression (direct suppression of CTLs)- Factors such as TGF-beta and PD-L1 secreted by tumour cells inhibit cells directly

Answer 37

modulation

Question 38

Homeostatic mechanisms aimed at preventing excessive inflammation and tissue damage

Answer 38

Immunological checkpoints. Immune checkpoints prevent the immune response from completely eliminating the pathogen or destroying the tumour.

Question 39

What is a CAR-T cell?

Answer 39

Chimeric antigen receptors which have been engineered to graft an arbitary specificity to an effector cell (T cell)  CARs include three parts: an extracellular antigen recognition domain of the single-chain Fragment variant (scFv) derived from an antibody), a transmembrane domain and an intracellular T cell activation domain of CD3ζ 

Question 40

How are the CAR-Ts introduced?’ | Two ways to accomplish gene incorporation with vectors:

Answer 40

Viral and Non-viral

Question 41

How do CAR-T’s work?’

Answer 41

works by triggering the immune system to recognize tumours and thus activates cancer cell lysis

Question 42

Structure of a CAR-T ScFv -an antibody fragment replacing the TCR which will recognize the tumor associate antigen (TAA) ___ is the signaling domain that will activate the immune response once the antigen bind to the scFv

Answer 42

CD3

Question 43

Side effects of immunotherapies

Answer 43

Complicated by severe immunosuppression/ cytokine release syndromes

Question 44

Immune evasion mechanisms by tumours include reduced tumour antigen presentation and local immunoregulatory factors: inhibitory ________ and cells

Answer 44

cytokines