Tumor Immunology

Question 1

Cancer accounts for ___% of death in industrialized countries

Current treatments include:

Answer 1

20%

Surgery, radiation, chemotherapy

Question 2

Types of carcinogens that induce mutations in DNA

Answer 2

Chemical

Radiation

Oncogenic

Question 3

Accumulation of mutations that leads to cancer cells (pathway)

Answer 3

1. Lost APC (suppressor gene) = Excessive proliferation
2. RAS activated (oncogene) = Small benign tumor
3. DCC lost = Large tumor
4. p53 lost = Invasive tumor
5. rapid accumulation of mutations = metastasis

Question 4

BRCA1/2 is a type of mutation that results in…

Answer 4

Reduced DNA stability or cell growth

Question 5

Lifespan of a typical tumor

Answer 5

First visible at 25 doublings (10⁸ cells)

First palpable at ~30 doublings (10⁹ cells)

Death at 10¹² cells

Question 6

Adenoma cells are more likely to _________

Answer 6

remain within a fibrous connective tissue capsule

Question 7

Define

• Carcinoma
• Leukemia
• Lymphoma
• Myeloma
• Sarcoma

Answer 7

Carcinoma = epithelial cell

Leukemia = circulating cell

Lymphoma = solid tumor in LN

Myeloma = Bone marrow cell

Sarcoma = Connective Tissue cell

Question 8

Some viral proteins induce unchecked proliferation of human cells by blocking ___ and ____

Answer 8

P53 and Rb

(tumor suppressor genes)

Question 9

Whether or not tumor cells from a person grow in another person depends on _________

Answer 9

the MHC haplotype of donors and recipients

Question 10

Tumor cells isolated from primary tumor in a MHC-a mouse effect when injected into:

1. another MHC-a mouse
2. A MHC-b mouse

Answer 10

1. Tumors grow, animal dies
2. Tumor rejected, animal lives

Question 11

What cells detect tumor cells?

Answer 11

• CD4
• CD8
• NK cells
• B cells

Question 12

T and B cells look for ________, which are differentially expressed by tumor cells and normal cells

Answer 12

tumor antigens

Question 13

Changes in the genome of tumor cells can lead to __________

Answer 13

the expression of tumor antigens

Question 14

Difference between tumor specific antigens and tumor associated antigens

Answer 14

Whether they are ONLY expressed or just TEND TO BE expressed by tumor cells

Question 15

NK cells kill what cells?

Answer 15

MHC-I-negative or Ab-coated tumor cells

Question 16

5 Tumor antigen classes that are recognized by CD8 T cells

(and examples of each)

Answer 16

Embryonic = MAGE-1,3

Abnormal PostTransMod’s = MUC-1

Differentiation = Tyrosinase

Mutated oncogene or tumor suppressor = B-catenin, Caspase-8

Oncoviral protein = HPV (E6 and E7 proteins)

Question 17

Peptide antigens: Disease + Antigens

• MART2
• ME1
• p53
• KIAA0205
• Triphosphate isomerase
• BCR-ABL fusion protein

Answer 17

• MART2 = Melanoma (A1)
• ME1 = Non-small cell lung carcinoma (A2)
• p53 = Head/Neck Squamous cell carcinoma (A2)
• KIAA0205 = Bladder tumor = B44
• Triphosphate isomerase = Melanoma = DR1
• BCR-ABL fusion protein = CML = DR4, B8, A2

Question 18

Fusion proteins result in _______

Answer 18

New epitopes

Question 19

Two functions of Antibodies to tumor cells

Answer 19

1. facilitate NK cell-mediated lysis of tumor cells
2. activate complement reaction

Question 20

Two ways that tumor cells activate the CD8 T cell

Answer 20

Antigens presented to T cell by APC (with costimulator)

APC activates CD4 helper T cell to release cytokines, which activate CD8

Question 21

Effector phase of anti-tumor CTL response

Answer 21

Tumor specific CD8 CTL recognizes tumor cell and kills it

Question 22

Tumor antigens can be presented via _____ which results in activation of…

Answer 22

MHC1

Both B cells and T cells

Question 23

6 examples of tumor evasion of immunity

Answer 23

1. out-growth of antigen-negative variants
2. Loss of MHC proteins
3. secretion of immunosuppressive cytokines
4. inducing CTL apoptosis
5. lack of co-stimulatory signals
6. soluble tumor antigens (“tolerance)

Question 24

example of an immunosuppressive cytokine produced by tumor cells

Why do these work for tumors?

Answer 24

TGF-beta (and TH2 cytokines)

We need the TH1 cell response to fight the cancer

Question 25

What do tumor cells shed to avoid NK cells?

Answer 25

**MHC class I-related chain (MIC)** a ligand of NKG2D (an activating NK cell receptor)

Question 26

Tumors also produce ____ which serves two functions: \_\_\_\_\_ Treg cells \_\_\_\_\_\_ TH1 cells

Answer 26

_TGF-β1_ * Induces Treg cells * Inhibits Th1 cells

Question 27

Treatment for superficial bladder cancer? Why does this work?

Answer 27

**BCG vaccine** (acts as adjuvant for immune response) It works b/c it activates APC's and other cells via **_TLR's_** (also induces _costimulation molecules_ and _MHC molecules_ on APC's)

Question 28

Four promising immunotherapies against tumor cells

Answer 28

1. **Antibody against tumor antigen** (immunotoxins and induction of ADCC by NK cells). 2. **Tumor vaccines**: express B7, GM-CSF or IL-12 in tumor cells. Tumor antigens can be used as vaccines too. e.g. CEA (carcinoembryonic antigen), HSP (heat shock protein), and telomerase 3. **Dendritic cell therapy**: dendritic cells are isolated from patients and are loaded with tumor antigen peptides in vitro. 4. **T cell therapy**: patients T cells, activated in vitro with tumor antigens and cytokines (IL-12), are injected back to the patients.

Question 29

5 Methods used for tumor vaccines

Answer 29

1. Killed tumor cells 2. Purified tumor antigens 3. DC's pulsed with tumor antigens 4. Plasmid DNA immunization 5. DC's transfected with plasmid expressing a tumor antigen

Question 30

therapeutic cancer vaccine for prostate cancer

Answer 30

**Sipuleucel-T** .Patient's blood --\> **DC's** + fusion protein consisting of the antigen **prostatic acid phosphatase** (PAP) and **GM-CSF**

Question 31

Monoclonal antibodies for cancer therapy (4)

Answer 31

**Rituxan** = Anti-CD20 (targets B cells) **Herceptin** = Anti-EFG-receptor-2 (a.k.a. HER2) **Erbitux** = anti-EGFR (HER1) **Avastin** = blocks VEGF receptor

Question 32

Radiolabeled antibodies approved by the FDA to detect cancer (2)

Answer 32

OncoScint, ProstaScint

Question 33

Immunization with MAGE-1/3 induces...

Answer 33

anti-melanoma immune response

Question 34

Rituximab target

Answer 34

CD20

Question 35

Traztuzumab target

Answer 35

HER2

Question 36

Alemtuzumab target

Answer 36

CD52

Question 37

Cetruximab target

Answer 37

EGFR

Question 38

Panitumumab target

Answer 38

EGFR

Question 39

Bevacizumab

Answer 39

VEGF

Question 40

Gemtuzumab target

Answer 40

CD33

Question 41

Ibritumomab and Tositumomab target

Answer 41

CD20

Question 42

Monoclonal antibodies to tumor antigens can deliver \_\_\_\_\_or ____ to tumor cells

Answer 42

Toxins or NK cells