Tumor Immunology

Question 1

2 hit hypothesis for cancer to form

Answer 1

*cells must undergo multiple mutations to become cancerous
*both tumor suppressor genes lost, oncogenes activated, sequential mutations, etc

Question 2

necessary characteristics of cancer cells

Answer 2

*stimulate their own growth
*ignore growth-inhibiting signals
*avoid death by apoptosis
*angiogenesis (develop their own blood supply)
*metastasis (invade other tissues)
*replicate continuously
*evade or outrun the immune response

Question 3

causes of cancer

Answer 3

*inherited mutations
*spontaneous mutations
*chemical or radiation-induced mutations
*dysregulation induced by certain oncogenic viruses

Question 4

viruses associated with human cancers

Answer 4

*HPV
*hep B
*Epstein-Barr
*HTLV-1
*HHV-8
*HIV-1

Question 5

immunogenic tumors

Answer 5

the ability of a tumor to induce an immune response that can prevent its growth

Question 6

tumor mechanisms of immune evasion

Answer 6

1) low immunogenicity
2) tumor treated as self antigen
3) antigenic modulation
4) tumor-induced immune suppression
5) tumor-induced privileged site

Question 7

low immunogenicity - tumor mechanism of immune evasion

Answer 7

*no peptide:MHC ligand
*no adhesion molecules
*no co-stimulatory molecules

Question 8

tumor treated as self-antigen - tumor mechanism of immune evasion

Answer 8

*tumor antigens taken up and presented by APCs in absence of co-stimulation TOLERIZE T cells

Question 9

antigenic modulation - tumor mechanism of immune evasion

Answer 9

*antibody against tumor cell-surface antigens can induce endocytosis and degradation of the antigen
*immune selection of antigen-loss variants

Question 10

tumor-induced immune suppression - tumor mechanism of immune evasion

Answer 10

*factors secreted by tumor cells INHIBIT T cells directly
*induction of regulatory T cells by tumors
**PD-L1

Question 11

tumor-induced privileged site - tumor mechanism of immune evasion

Answer 11

factors secreted by tumor cells create a PHYSICAL BARRIER to the immune system

Question 12

3 methods of augmenting the anti-tumor response

Answer 12

1. prophylactic and therapeutic vaccination
2. using biologics to deplete tumor cells
3. turning inhibitory circuits off

Question 13

prophylactic and therapeutic vaccination to increase anti-tumor response

Answer 13

1. prophylactic vaccinations (ex. make antibodies after receiving HPV vaccine protects you from cancer)
2. therapeutic vaccinations (driving APCs to prime T cells that will attack the tumor)

Question 14

antibody-mediated tumor therapy

Answer 14

a tumor-specific antibody will bind to the tumor cells and NK cells, driving killing of those tumor cells

Question 15

important example of antibody-mediated tumor therapy - Rituximab

Answer 15

*antigen = CD20 (B cells)
*function of antigen = B-cell signaling receptor
*treats Non-Hodgkin’s Lymphoma

Question 16

important first generation immunotherapies for augmenting anti-tumor responses

Answer 16

blocking antibodies against:
*CTLA-4 receptor
*PD-1 receptor

Question 17

PD-1:PDL-1 interaction

Answer 17

*PDL1 produced by the tumor cell binds PD1 of the host T cell, downregulating the activity of T cells and the immune system
*BLOCKING this interaction (anti-PD1) TURNS THE INHIBITORY CIRCUIT OFF, keeping the immune response going

Question 18

CTLA-4 antibody for tumor therapy

Answer 18

*B7 of the APC binds CTLA-4 produced by the T cell to downregulate the activity of T cells and the immune system
*BLOCKING this interaction TURNS THE INHIBITORY CIRCUIT OFF, keeping the immune response going