The Role of immune system in Cancer Flashcards Preview

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Flashcards in The Role of immune system in Cancer Deck (52)
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1
Q

what can the immune system do in terms of tumour progression

A
  • it can facilitate or inhibit tumour progression
2
Q

How does the immune system protect us against cancer

A

via immune surveillance

3
Q

descirbe how immune surveillance can protect us against cancer

A

Tumor cells and tumor antigens initiate the release of “danger” cytokines (IFN and heat shock proteins (HSP))
.
Activation and maturation of dendritic cells to present tumor antigens to CD8 and CD4 cells

subsequent T cytotoxic destruction of the tumor

4
Q

How can cancer evade the immune response

A

Tumor antigens are weakly immunogenic

Often self antigens, potential tolerance

Cancer cells have evolved mechanisms to prevent immune rejection

5
Q

name the ways in which the cancer cells have evolved to prevent immune rejection

A

Secretion of inhibitory cytokines

Creation of unique microenvironment - sits and organises in a way that it can grow and become more malignant and is protected from the immune system

Alteration of host immune system locally and systemically

Induction of inhibitory T cell subsets

6
Q

describe how cancer can escape from the immune system

A
  • the immune system normally eliminates the cancer and this is effective immune surveillance
  • but someones the cancer can escape from the immune system and this leads to rapid proliferation of resistance clones
  • this develops over several years
7
Q

What immune cell is important to have in order for long term survival in cancer

A
  • Many T regs are important to have as these cancers can be controlled fro a longer period of time versus people who have fewer T regs
  • if you have fewer T reg cells the cancer is more aggressive
8
Q

What is progression free survival

A

The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse

9
Q

what family of T cells is T reg from

A

CD4 positive T cells

10
Q

what is the role of T reg cells

A
  • regulating the immune response through antigen specific suprpession of effector CD4+ and CD8+ T cells
11
Q

what are the two molecules that T reg cells express

A

Most Treg cells express CD4/CD25high and FOXP3

12
Q

In what cancers in particularly do T reg cells predict survival in

A

Specific recruitment of regulatory T-cells in ovarian carcinoma and follicular lymphoma fosters immune privilege and predicts survival

13
Q

Why are T cells in cancer exhausted

A

T cells in cancer are exhausted due to chronic stimulation by cancer (e.g. CLL).
• Important marker: PD1 (increased on cell surface).

14
Q

What is cancer immunology

A

Cancer immunology is the study of how cancer affects the host immune system, focusing on how cancer evades immune destruction

15
Q

What are the 3Es of immunoediting

A
o	Elimination (immune system eliminated cancer cells)
o	Equilibrium (cancer cells co-exist with immune system)
	Immune cells kills of majority of cells, but some of the cells evolve to escape immune system.
o	Escape (cancer cells escape the immune system).
16
Q

What are the two types of cancer immunotherapy

A
  • Passive

- Active

17
Q

Describe passive immunotherapy

A
  • administration of agent for example as a monoclonal antibody, transfer or effector cell, T cells, NK cell, regulatory cells
18
Q

describe active immunotherapy

A
  • Induction of host immune response for example by a vaccination or adjuvant treatment
19
Q

describe how monoclonal antibodies are produced

A

To create mAbs, human cancer cells were injected into mice.

In response, the mouse immune system makes antibodies against these cancer cells.

Mouse plasma cells produce antibodies were fused with laboratory-grown cells to create “hybrid” cells called hybridomas.

Hybridomas indefinitely produced large quantities of these pure antibodies, or mAbs.

20
Q

what are mouse and human monoclonal antibodies called

A

chimeric (-imab)

21
Q

What are fully humanized antibodies called

A

fully humanized (-umab)

22
Q

How do you approach using monoclonal antibodies for treatment

A

o Unconjugated: complement mediated lysis.
o Coupled to toxins: immunotoxins.
o Coupled to radioisotopes: radioimmunoconjugates (radiation theraphy).
o Also to cells surrounding it.

23
Q

What is the major problem with monoclonal antibodies

A

Major problem with murine mAbs was that patients developed human anti-mouse antibodies (HAMA) so that these agents could be used only once.

24
Q

in a mouse and human monoclonal ab what part is human and what part is mouse

A

Binding site is murine

backbone is human

25
Q

describe how humanisation of monoclonal abs have taken place

A

Recent advances to develop recombinant molecules that maintain the antigen binding of the murine mAb coupled to the human Ig backbone, a process known as “humanization” of a mAb has revolutionized this field

26
Q

What is the ideal target for monoclonal antibody therapy

A

Expressed on all tumor cells

  • Not present on critical host cells
  • No significant toxicity if all antigen+ cells eliminated
  • High copy number
  • No mutations or variant antigens
  • Required for critical biologic function or cell survival
  • Not shed or secreted
  • Not modulated after antibody binding
27
Q

name three proposed mechanism of action of monoclonal Abs

A

Antibody-dependent cell-mediated cytotoxicity (ADCC)

Complement-dependent cytotoxicity (CDC)

Apoptosis

28
Q

Describe how complement dependent cytotoxicity works (CDC)

A
  • uses a membrane attack complex(MAC) and beta cell lysis
  • there is a sequential activation of remaining complement components which leads to incorporation into the MAC
  • The MAC then forms a pore through the target cell membrane and causes lysis
29
Q

describe how monoclonal antibodies induced ADCC ( antibody dependence cell mediated cytotoxicity)

A

 Fc region on phagocytic cells e.g. NK cells, macrophages, neutrophils.
 Effector cells  release mediators that damage and destroy malignant B cells.
 Malignant B cells are phagocytosed.

30
Q

describe how monoclonal abs directly induce B cell apoptosis

A

mAb binding to CD20 may induce transmission of intracellular signals that trigger cell cycle arrest and apoptosis

31
Q

What is rituximab used to treat

A

single agent in patients with relapsed non-Hodgkin’s lymphoma

32
Q

describe Rituximab as a monoclonal ab

A

Chimeric MoAb that targets protein called CD20 that is present on the surface of normal and malignant B cells

33
Q

What is trastuzumab used for

A

HER2 positive breast cancer

34
Q

How is trastuzumab afforded

A

cancer drug fund

35
Q

What is a bi specific monoclonal ab

A

MoAb which is designed to bind to two different antigens

 E.g. CD19/CD3 bispecific antibodies.

36
Q

give an example of a bi specific monoclonal ab

A

blinatumomab

37
Q

How do Bi specific monoclonal abs work

A

CD8 positive T cell recognizes an antigen in coordination with MHC 1 which every cell has
tumour antigen is too weak to activate the T cell

if there is a bi specific monoclonal antibodies can grab the T cells and activate it to defend against the antigen

38
Q

when are prophylactic cancer vaccines given

A

Prophylactic vaccines are given to healthy individuals before cancer develops.

39
Q

what are prophylactic cancer vaccines designed to do

A

These vaccines are usually designed to stimulate the immune system to attack viruses that can cause cancer

40
Q

what certain cancers are targeted using vaccines

A

cervix and liver

41
Q

what are the current types of vaccines

A

Antigen/adjuvant vaccines

Whole cell tumor vaccines

Dendritic cell (DC) vaccines

Viral vectors and DNA vaccines

Idiotype vaccines.

42
Q

What is the mechanism of action of immunomodulators

A

• PD1 is highly expressed in the immune cells of cancer patients.
o These are inhibitory receptors.
• Balance between activing receptors and inhibitory receptors  immune response.
o Cancer cells overexpress checkpoint receptors.
 Poised to switch immune cells off

43
Q

What does blocking immune checkpoints promote

A

Blocking immune checkpoints may promote endogenous antitumor activity

44
Q

What are PD1 on T cell tumours associated with

A

PD1 expressed on T-cells when exposed to tumour, and associated with exhaustion.
Blocking these PD1 receptors can restore function

45
Q

When do PD1 act as inhibitory receptors

A

PD1: Inhibitory receptor on activated T-cells, B-cells, NK and myeloid cells.
Inhibition of T-cell activation when engaged by ligands (PDL1/2)

46
Q

How do immune checkpoints inhibitors work and give an example

A

• Blocking immune checkpoints may promote endogenous antitumor activity
o Eg. Blocking of PD1 can restore function of T-reg cells.

47
Q

How do you treat Chronic Lymphocytic Leukaemia displaying PD1

A

by inhibiting PD1

48
Q

What cancers is PD-L1 expressed in

A
  • Non small cell lung cancer (squamous cell carcinoma)
  • Non small cell lung cancer (adenocarcinoma)
  • colon
  • melanoma
  • renal
49
Q

What two cancer types make up non small cell lung cancer

A

squamous cell carcinoma

adenocarcinoma

50
Q

What is the approved treatment used for PD1 (checkpoint inhibitors) today

A

PD1 inhibitors;

  • Nivolumab
  • Pembrolizumab
51
Q

What is a chimeric antigen receptor

A

The chimeric antigen receptor is then added to immune cells called T cells. This helps the T cells find and kill cancer cells that have the specific protein that the receptor is designed to bind.

52
Q

Describe the theory behind how chimeric antigen receptors work

A

= usually T cells cannot recognise an antigen without MCH1
= the chimeric antigen receptor helps the T cell recognise the cancer cell and therefore cause the cancer cell to be killed by the T cell