Tumor Immunology

Question 1

How do tumor cells evade the immune system?

Answer 1

1. Produce self Ags
2. Suppress activation of cell mediated immunity
3. Suppress MHC
4. Activate regulatory T cells
5. Shed to limit surface expression of potential Ags (appear normal)

Question 2

What do tumor cells have the ability to do?

Answer 2

Indefinitely and rapidly replicate
Defy cell death
Not require external GFs
Metastasize
Gemonic instability and mutation

Question 3

Major tumor anitgens

Answer 3

1. Arising from mutation
2. Inappropriate expression (expressed after embryonic stages when it was supposed to stop)
3. Over expressed compared to normal cell (GF in breast cancer)

Question 4

What cells are involved in immunity to tumors?

Answer 4

Macrophages
Antibody dependent cellular cytotoxicity (ADCC)
Natural Killer cells
CD8+ (attack MHC-dependently)

Question 5

When is antibody dependent cellular cytotoxicity released?

Answer 5

If Abs produced against surface antigens
Works for blood cancers

Question 6

How is the immune system activated against cancer?

Answer 6

Immune stimulants
Immunotoxins
LAKs
Checkpoint inhibition

Question 7

Immune stimulants examples

Answer 7

Cytokines (INF, TNF, IL-2 GMCSF)
Bacterial products (BCG)

Question 8

Immunotoxins

Answer 8

Abs against tumor (alone or conjugated to toxin)

Question 9

LAKs (Lymphokine activated killers)

Answer 9

Take out lymphocytes and activate in virto then inject back

Question 10

Checkpoint inhibition

Answer 10

Stimulate T-cell through blockage of inhibitory signals
Ex: checkpoint blockade immunotherapy (risky)

Question 11

T-cell therapy

Answer 11

Type of immunotherapy
Remove T cells, stimulate or engineer ex vivo and return (LAK, CAR cells)

Question 12

Active Immunization

Answer 12

Type of immunotherapy
Uses immune stimulants
No active vaccine on the market
Ex: BCG and other adjuvants

Question 13

First tumor vaccine?

Answer 13

Oncept which targets the (human) tyrosinase protein in melanoma
Human or murine gene injected

Question 14

Ab success

Answer 14

Limited, only mAbs for some B cell (Blontress against CD-20) or T cell lymphoma (Tactress, against CD-56) approved by USDA

Question 15

Lymphoma in dogs medication

Answer 15

Repeated infusions of autologous lymphocytes expanded ex vivo with an anti-CD3 mAb and human cytokines IL-2 and IL-21 (post chemotherapy)

Question 16

What animals tumor are relevant to immunity or immune cells?

Answer 16

Injection site sarcomas
Transmissible venereal tumor/ sarcoma
Bovine lymphosarcoma
Marek disease and Avian Lymphoid Leukosis

Question 17

Injection site-associated sarcomas

Answer 17

They develop in 1/10,000 or less cat vaccines
Tumor develop @ injection site years later
Main factor is local chronic irritation (pro-inflammatory cytokine IL-23)

Question 18

Transmissible Venereal Tumor (TVT, TVs)

Answer 18

Tumor transmitted between dogs during copulation (tumor cells transmitted and implanted)
TVT all over the world originates from one source (clones)
Agreessive tumors don’t express MHC-1 on surface

Question 19

Bovine lymphosarcoma/ Bovine viral leukosis

Answer 19

Involves primarily B cells: lymphocytosis
Common tumor >44% in dairy and >10% in beef
5% develop a clinical disease
Animals immunosuppressed (reduced T cells)

Question 20

What is Bovine lymphosarcoma caused by?

Answer 20

Retrovirus Bovine leukemia Virus (BLV) transmitted by infected lymphocytes (injections, flies, blood products, in utero, colostrum, etc)

Question 21

Marek disease

Answer 21

Herpes virus induced T-cell tumor of chickens
Disease birds immunosuppressed
Vaccine available

Question 22

Avian lymphoid leukosis

Answer 22

B-cell lymphoma induced by Avian Leukosis viruses
No vaccine
Disease birds immunosuppressed