immunology 5: tumour immunology

Question 1

immune surveillance

Answer 1

by T cells

Question 2

TILs

Answer 2

tumour infiltrating lymphocytes are present in tumour microenvironment

of TILs = correlates with overall survival

Question 3

function of TILs

Answer 3

recognise TAA (tumour associated antigens)

detection of under expressed proteins e.g. lack of MHC 1

Question 4

TAA

Answer 4

are changes in surface proteins expressed on MHC as a result of tumorigenic process

can be tumour specific or tumour associated

tumour specific = neoantigens

Question 5

neoantigen MAGE1

Answer 5

melanoma expresses several tumour antigens

example: MAGE-1 is a germ cell protein found in testes (immune privileged) so T cells will react to MAGE 1 as they have not previously encountered this protein

Question 6

immunocytes in the anti tumour immune response

Answer 6

NK cells
CD8 + T cells
Antibodies
NK cells
macrophages
CD4+ T cells

Question 7

CD8 + T cells in anti tumour response

Answer 7

become activated by tumour antigen/MHC combination

intracellular cytotoxic granules containing perforin and granzyme B

granzyme cleaves caspases in target cell which induces apoptosis

Question 8

NK cells in anti tumour response

Answer 8

NK cells distinguish between infected/stressed cells from healthy cells via loss of MHC I molecule on cell

kill infected cells using perforin + granzyme

Question 9

antibodies in anti tumour response

Answer 9

antibody induction of complement cascade

ADCC mediated cell death = antibody dependent cell mediated cytotoxicity

Question 10

ADCC = antibody dependent cell mediated cytotoxicity

Answer 10

both NK cells and antibodies required to activate this mechanism

ADCC by antibodies + NK cells act together

antibody binds to antigens on tumourigenic cell and NK cells are signalled

Fc receptors on NK cell recognise bound antibody Fc

when enough of Fc receptors are recognised, the NK cell will become activated and kill target cell

NOTE: target cell will die by apoptosis

Question 11

tumour cells evading the immune system

Answer 11

1. decreased antigen presentation via suppressed MHC I
2. suppressing the immune response:
   > signal T cells to shut off
   > expression of PD-L1 which acts as a ligand for T cell receptor PD-1. When these come together the t cell shuts off
   > secrete anti inflammatory cytokines e.g. IL -10, TGF beta
   > attract Treg cells to tumour site
3. outpacing the immune response

Question 12

cancer immunotherapy

Answer 12

1. prophylactic vaccination
2. dendritic cell vaccines
3. adoptive T cell transfer/Car T cell therapy
4. passive immunotherapy with monoclonal antibodies
5. immune checkpoint inhibitor therapies

Question 13

adoptive T cell transfer

Answer 13

some of tumour mass is removed and isolated to allow for TIL to be isolated and expanded in vitro

at the same time the patient is undergoing chemotherapy/radiotherapy to regress the tumour slightly

the TILs along with active cytokines are administered back to patient

Question 14

passive immunotherapy with monoclonal antibodies

Answer 14

induces complement mediated lysis of tumour cells and ADCC e.g. herceptin and HER2 receptor

Question 15

immune checkpoint inhibitor therapies

Answer 15

blocking PD-1/PD-L1 interaction

an antibody can bind to PD-1 on T cell blocking it from binding to PD-L1

monoclonal antibodies anti PD-1 or PD-L1 will shut off mechanism from happening