Tumor Immunology (31)

Question 1

Which features are cancers defined by?

Answer 1

abnormal cell proliferation —> loss of normal regulatory features that limit growth

ability to spread to other portions of the body through metastases

resist cell death

induce angiogenesis

ability to avoid immune destruction

Question 2

T/F: Cancer is more common in patients with suppressed immune systems

Answer 2

TRUE

Question 3

List two types of people to be more prone to cancer (we have discussed)

Answer 3

those on immunosuppressives following organ transplants

long-term graft survival

Question 4

___ activation contributes to malignancy in a population

Answer 4

T-cell (cell-mediated)

Question 5

What is immunosurveillance?

Answer 5

recognition of tumor cells by the immune system requires the presence of “foreign” antigens or “tumor-specific antigens” to overcome self-tolerance

Question 6

What are tumor antigen examples?

Answer 6

CD antigens
tyrosinase
c-kit
PSA
FOCMA

Question 7

Because these tumor antigens are unique to tumors, they can be targeted by _____

Answer 7

immunotherapies

Question 8

What are the classifications of tumor antigens?

Answer 8

differentiation antigens
excessive amounts of normal proteins
mutated proteins
cancer/testis antigens
viral-coded proteins

Question 9

What are tumor antigens?

Answer 9

mutated self-proteins that may or may not contribute to tumor progression - aberrant proteins (bcr-abl, c-kit mutants

overexpressed proteins (tyrosinase)

development or tissue restricted proteins

CD antigens

oncogenic viral proteins

Question 10

What are CD antigens?

Answer 10

define specific leukocyte subsets

monoclonal antibodies are available to target many CD antigens

Question 11

Where is c-kit normal found expressed on?

Answer 11

canine mast cells

Question 12

What is c-kit?

Answer 12

membrane-associated signaling protein

important for stem cell maturation

promotes growth and differentiation

Question 13

What is a feature of c-kit that causes a poor outcome? It causes [increased/decreased] membrane expression

Answer 13

aberrant expression (found in places it shouldn’t be found)

decreased

Question 14

Regarding c-kit, a tumor-associated antigen, _____ & ______ allows selective tumor targeting - small molecule inhibitors that block activation site in kinase

Answer 14

overexpression
mutations

Question 15

What is tyrosinase? It’s expression is limited to ______

Answer 15

tumor-associated antigen

melanosome-associated glycoprotein that is critical for melanin production

melanocytes

Question 16

Tyrosinase is [up/down]-regulated in developing _____ and turned off in quiescent ______

Answer 16

up
melanocytes
melanocytes

Question 17

What are the most effective immune response to target tumors?

Answer 17

CTL
NK cell responses

Question 18

Why aren’t more patients cured of tumors?

Answer 18

immune responses often fail to eradicate tumors because the tumors develop mechanisms to evade immune regulation

tumors may grow more rapidly than the immune system can handle

develop mechanisms to evade the immune system - such as resistance

Question 19

_____ proteins may be weakly immunogenic and thus able to evade the immune system

Answer 19

Aberrant

Question 20

Immune _____ is common in humans and dogs with cancer

Answer 20

dysfunction
(have bad CD8 to Treg ratios)

Question 21

How does immune evasion occur?

Answer 21

reduced or absent expression of tumor antigens

reduced or absent MHC I expression

inhibition of CTL activation

upregulate CTLA-4: transmits inhibitors signal to B7 costimulator

Question 22

Tumors that express high levels of _____ inhibit T cell activation

Answer 22

PD-L1

(gilvemab blocks this PD-L1/2 pathway)

Question 23

Which cytokine is dysregulated in advanced tumors and promote tumor growth?

Answer 23

TGF-beta

• high levels in epithelial tumors

Question 24

Which cytokines from Treg affect immune response?

Answer 24

IL-4, IL-6, IL-10

Question 25

What ratio is disrupted in cancer patients and is increased?

Answer 25

CD4+FoxP3+ T-

CD8/Treg ratio is prognostic for survival

Question 26

What are the 3 general strategies used for tumor treatment?

Answer 26

non-specific immune stimulants

passive immunotherapy

active immunotherapy

Question 27

What are immune strategies used to target tumors - non-specific immune stimulants?

Answer 27

cytokine therapy
- IFN-alpha, IFN-beta, IFN-gamma

Question 28

What are passive immune stimulants?

Answer 28

in vitro-primed T cell therapy

monoclonal antibody therapy

Question 29

What does monoclonal antibody therapy target?

Answer 29

vascular stroma, tumor antigens, membrane death receptors

developed to treat many solid and hematogenous cancers