Lecture 8: Cytokines and Cancer

Question 1

Stromal cells

Answer 1

Any cells around the tumor

Question 2

Tumor infiltrating lymphocytes (TIL) role in cancer

Answer 2

strongly correlated with survival in several cancer types

the more TIL, the higher the survival

Question 3

3 cytokine functions

Answer 3

1. Endocrine action (circulation to distant cells)
2. Paracrine action (nearby cells)
3. Autocrine action (stimulate itself)

Question 4

4 properties of cytokines

Answer 4

1. Pleiotropic (multiple effects)
2. Redundant
3. Synergistic
4. Antagonistic

Question 5

Cytokines cascade

Answer 5

activation of one cytokine produced by one cell type induce cytokine production by other cell types

Question 6

Structure of cytokine receptors

Answer 6

consist of one or more transmembrane protein

extracellular: cytokine binding
cytoplasmic: initiation of intracellular signalling pathways

Question 7

4 types of cytokine receptors

Answer 7

Type 1

Type 2

TNF receptor family

IL-1/TLR family

Question 8

Cytokine receptor family function

Answer 8

must be dimerized

form reception complex with ligand

lack intrinsic kinase activity but associate with intracellular kinase

Question 9

Innate immunity

Answer 9

first line of defense against infection

granulocytes, mast cells, macrophages, dendritic cells and natural killer cells

Question 10

Adaptive immunity

Answer 10

mediated by antibodies and CD4 and CD8 T cells

Question 11

Perforin and IFN-y double knockout mices

Answer 11

susceptible to spontaneous lymphomas

Question 12

Compromised FAS-FAS ligand mices and function of FAS

Answer 12

FAS (TNF family receptor) (death receptor) helps to maintain B-cell and T-cell homeostasis

frequently form B-cell lymphomas

Question 13

Rag2/Stat1 double knockout mice

Answer 13

regularly develop adenocarcinomas of the colon, breast and lung

Question 14

GM-Csf/ IFN-y knockout mice

Answer 14

develop diverse blood and solid cancers with chronic infection

Question 15

Cytokine therapies and the associated adverse effect

Answer 15

Systemic administration

stimulate anticancer responses

can lead to CYTOKINE STORM

Question 16

IFN-a

Answer 16

induce NK cells and DC against tumor cells to inhibit cell proliferation and kill cancer cells

Question 17

IL-1a

Answer 17

cytotoxic-cytostatic activity against refractory malignancies and solid tumor cells

Question 18

IL-2

Answer 18

anticancer against hematologic malignancies (leukemia and lymphoma) in vitro, in vivo and clinical studies

Question 19

IL-7

Answer 19

combination with human T-cells showed significant anticancer activity in human colon carcinoma via activation of the PI3K/AKT pathway

Question 20

Mechanism of immune evasion

Answer 20

1. loss of antigenicity
2. loss of immunogenicity
3. immunosuppressive microenvironment

Question 21

CTLA-4

Answer 21

expressed by activated T cells and DC

inhibit signals to T cells

can be targeted by monoclonal antibodies to activate immune system

Question 22

PD-L1 and PD-1

Answer 22

found on activated T cells

inhibits activation of IL-2 production and T cells proliferation

target and inhibit PD-1 receptor to reduce cancer evasion

Question 23

Tumor infiltrating lymphocytes (TIL) therapy

Answer 23

remove TIL from patients

cultured with IL-2 to induce proliferation

infused back to patient and help immune system to kill cancer

performed in advanced (cutaneous) melanoma

antitumor activity in other solid tumor still remains a challenge

Question 24

Car T-cells therapy

Answer 24

T cells collected from patient

insert gene to help locate antigens or proteins on the surface of cancer cells

infused back and allow T-cells to target and destroy cancer cells

Question 25

T-cell receptor therapy (TCR)

Answer 25

T cells collected from blood

gene inserted to find specific cancer antigen or protein

infused back to patient to launch attack against cancer

Question 26

In vitro sensitized (IVS) T-cell therapy

Answer 26

T-cells collected from blood

taught to recognize cancer cells through ex vivo activation (no genetic change)

multiplied and returned through infusion

Question 27

Cytokine release syndrome

Answer 27

when tumor is destroyed, its releases large quantities of cell signalling protein molecules

the effect killed at least seven patients