I3 Tumor Immunology and Immunotherapy

Question 1

The study of mchanism used by the immune system to monitor and control the developement of neoplastic cell populations
The investigation of means to apply those mechanisms in tumor immunotherapeutic approaches
The mechanisms used by tumors to evade the immune response

Answer 1

Tumor Immunology

Question 2

The concept that immune system surveys self tissues for malignany (and pre-malignant) cells and decreases development of cancer. Supported by studies that cancers are more prone to deelop when immunodeficent.

Answer 2

Immunosurveillance

Question 3

The concept that immune system selective pressure may result in development of tumors that are less immunogenic over time.

Answer 3

Immune editing

Question 4

The concept that becuase of immune editing, tumors that ultimately develop have evolved mechanisms to evade an effective immune response.

Answer 4

Immune evasion

Question 5

Down regulate MHC class I expression leading to less KIR inhibition
Express ligands for NK cell activating receptors

Answer 5

Natural Killer cells

Question 6

Fxn as APC that activate T cells

Fxn as cells that produce cytokines and other biological mediators that potentiate and down regulate immune responses.

Answer 6

MØ and Dendritic Cells

Question 7

CD 20 CD 19 on B cell leukemia/lymphoma

Prostate specific acid phosphatase associated with prostate/melanocytes in melanoma

Carinoembryonic antigen and colon cancer

Over expression of HER2 antigen by tumor cells compared to normal cells in breast cancer

Answer 7

Examples of Tumor Associated Antigens

Question 8

antigens associated with tumors but may also be expressed by other non malignant cells

Answer 8

Tumor Associated Antigens

Question 9

antigens specifically associated with tumors but noth normal tissue

Answer 9

Tumor Specific Antigens

Question 10

protein product of oncogenes present in tumor cells like
bcr ABL mutations
kRAS mutations

Answer 10

Examples of Tumor Specific Antigens

Question 11

List the tumor evasion mechanisms.

Answer 11

1. Decreased TCR signal due to decreased expression of MHC molecules (decrease in ability of T cells to by stimulated by tumor cells)
2. Decreased/Lack of co stim. molecules by tumor cells or on APCs (more anergy bc TCR signal present but no co stim)
3. Activated of a negative co stim molecule (CTLA-4 and PD1)
4. Fox P3 T regulatory cells
5. Regulatory accesory and APCs in tumor environment that lack production of pro-inflam cytokines and have low co stimulatory molecule expression and may produce negative co stim molecules and suppressive cytokines

Question 12

negative co stim. molecule
Inhibits T cell activaion by interacting with B7 with a higher affinity than CD 28.
Serves to block CD 28 dependent signals.
Induces signalling events that inhibit TCR stimulation.

Answer 12

CTLA 4

Question 13

Abs that target CTLA 4 and block its engagment and promote initial T cell actiation and stimulation of effector T cells
This blockade of CTA 4 however is associated with autoimmue inflammatory complications

Answer 13

Ipilumamab

Question 14

negative co stim molecule
classical ITIM motif that is thought to induce signalling events that inhibit TCR stimlation. Blockade of PD 1 interaction with PDL -1 will promote tumor specific immune response.

Answer 14

PD1

Question 15

A therapeutic approach that consists of stimulating an endogenous immune response by exposrue to antigen (tumor antigens).
ex) HPV vaccine

Answer 15

Active vaccination

Question 16

a therapeutic approach
active vaccine approach + adoptive cell therapy where pt dendritic cells are cultured in vitro with a genetically engineered fusion protein of prostate acid phosphatase and GM-CSF and then transferred into the patient

Answer 16

Sipuleucel/Provenge

Question 17

adoptive immunotherapy

Answer 17

1. Passive immunization with monoclonal Ab
2. Adoptive transfer of tumor specific T cells
3. Transfer of polyclonal tumor specific T cells
4. Transfer of genetically modified tumor specific T cells ( genetic modification w/ T cell receptors specific for MHC/peptide complex AND genetic modification with chimeric antigen receptor)
5. Inhibitory Checkpoint blockade