(FE) Week 13 Tumor Immunology

Question 1

What is epigenetic erasure?

Answer 1

• Modifications to DNA are reset in cells, especially in early development
• Allows reset in order to change and adapt to new environmental conditions

Question 2

What are the mechanisms of DNA replication fidelity?

Answer 2

• Polymerase selection of nucleotides
  ~ To produce the correct proteins
• Proof reading of nucleotide chain
• Mismatch repair on making proteins

Question 3

What are the characteristics of tumor cells?

Answer 3

1) Not fully differentiated (due to accumulated mutations)

2) Lack of tissue-specific functions

3) Retain their growth potential (tf allowing them to grow uncontrollably)
- Faster growth than neighboring normal cells

4) Able to evade contact inhibition principle of cell growth in tissues

5) Increased mobility

6) Escape to invade neighboring tissuee, and metastasize to distant tissues

7) Evade immune system

Question 4

How do tumors progress?

Answer 4

1) Clonal expansion
- E-cadherin needed to send signals to high-density cells to stop proliferating
~ Known as contact inhibition
- LOSS/MUTATION of E-cadherin causes disrupted cell-cell adhesion and cells grow on top of each other

2) Local invasion
- When tumor cells continue to grow at site

3) Distant metastasis
- When tumor cells migrate to other parts of the body

Question 5

What are the classifications of cancers?

Answer 5

1) Carcinomas
- Tumors of epithelial cell origin (eg skin, mucosa, glands)

2) Sarcomas
- Cancer of connective tissue
- Eg Kaposi’s sarcome

3) Lymphomas
- Solid tumors of B/T cell origin

4) Leukemia
- Disseminated tumors of lymphoid or myeloid origin

Question 6

What happens to T cell activation when one of the 2 signals are missing?

Answer 6

• Missing MHC signal (Only co-stimulatory): No effect on T cell
• Missing co-stimulatory signal: T cell anergy

Question 7

Types of tumor antigen presented on CD8_ T cells?

Answer 7

• Product of oncogene/mutated tumor suppressor gene
• Overexpressed self protein
• Oncogenic virus

Question 8

What is immune checkpoint inhibition?

Answer 8

1) In LN
- APC activates T cells with tumor antigen
- After prolonged activation, T cells expresses CTLA4 to compete against CD28
~ Inhibits further activation

2) At tumor mass
- T cell moves to tumor mass to kill
- Tumor cell displays PD-L1 to PD-1 receptor on T cell which is produced when activation is prolonged
- T cell killing of tumor cell is inhibited

Question 9

What are the mechanisms of tumor evasion?

Answer 9

1) Failure to produce tumor Ag by MHC I to CTl

2) Mutation in MHC gene
- Prevents presentation of tumor Ag on MHC I

3) Tumors express surface inhibitory receptors or secrete inhibitory cytokines

Question 10

What are the options for cancer immunotherapy?

Answer 10

1) Inject cytotoxic cytokines

2) Tumor vaccines

3) Serotherapy
- Injecting monoclonal antibodes
- CD19/20

4) Adoptive T cell immunotherapy
- Tumor-infiltrating lymphocytes (TIL)

• Engineered chimeric antigen receptor T cells (CAR-T)

Question 11

How do dendritic cell vaccines work?

Answer 11

• DC pulsed with tumor Ag are injected into px
• APC presents tumor Ag to px’s tumor-specific T cells
• Activation of tumor-specific killing by T cells

Question 12

What are the MOA of rituximab against B cell lymphoma?

Answer 12

1) Direct killing (apoptosis)

2) Cell lysis due to complement cascade

3) Binds to NK cells to release granzymes and perforin to infected B cells

4) Binds to macrophages to phagocytose infected B cell