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Flashcards in Tumor Immunology Deck (42)
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1
Q

Cancer accounts for ___% of death in industrialized countries

Current treatments include:

A

20%

Surgery, radiation, chemotherapy

2
Q

Types of carcinogens that induce mutations in DNA

A

Chemical

Radiation

Oncogenic

3
Q

Accumulation of mutations that leads to cancer cells (pathway)

A
  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
4
Q

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

A

Reduced DNA stability or cell growth

5
Q

Lifespan of a typical tumor

A

First visible at 25 doublings (108 cells)

First palpable at ~30 doublings (109 cells)

Death at 1012 cells

6
Q

Adenoma cells are more likely to _________

A

remain within a fibrous connective tissue capsule

7
Q

Define

  • Carcinoma
  • Leukemia
  • Lymphoma
  • Myeloma
  • Sarcoma
A

Carcinoma = epithelial cell

Leukemia = circulating cell

Lymphoma = solid tumor in LN

Myeloma = Bone marrow cell

Sarcoma = Connective Tissue cell

8
Q

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

A

P53 and Rb

(tumor suppressor genes)

9
Q

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

A

the MHC haplotype of donors and recipients

10
Q

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
A
  1. Tumors grow, animal dies
  2. Tumor rejected, animal lives
11
Q

What cells detect tumor cells?

A
  • CD4
  • CD8
  • NK cells
  • B cells
12
Q

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

A

tumor antigens

13
Q

Changes in the genome of tumor cells can lead to __________

A

the expression of tumor antigens

14
Q

Difference between tumor specific antigens and tumor associated antigens

A

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

15
Q

NK cells kill what cells?

A

MHC-I-negative or Ab-coated tumor cells

16
Q

5 Tumor antigen classes that are recognized by CD8 T cells

(and examples of each)

A

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)

17
Q

Peptide antigens: Disease + Antigens

  • MART2
  • ME1
  • p53
  • KIAA0205
  • Triphosphate isomerase
  • BCR-ABL fusion protein
A
  • 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
18
Q

Fusion proteins result in _______

A

New epitopes

19
Q

Two functions of Antibodies to tumor cells

A
  1. facilitate NK cell-mediated lysis of tumor cells
  2. activate complement reaction
20
Q

Two ways that tumor cells activate the CD8 T cell

A

Antigens presented to T cell by APC (with costimulator)

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

21
Q

Effector phase of anti-tumor CTL response

A

Tumor specific CD8 CTL recognizes tumor cell and kills it

22
Q

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

A

MHC1

Both B cells and T cells

23
Q

6 examples of tumor evasion of immunity

A
  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)
24
Q

example of an immunosuppressive cytokine produced by tumor cells

Why do these work for tumors?

A

TGF-beta (and TH2 cytokines)

We need the TH1 cell response to fight the cancer

25
Q

What do tumor cells shed to avoid NK cells?

A

MHC class I-related chain (MIC)

a ligand of NKG2D (an activating NK cell receptor)

26
Q

Tumors also produce ____ which serves two functions:

_____ Treg cells

______ TH1 cells

A

TGF-β1

  • Induces Treg cells
  • Inhibits Th1 cells
27
Q

Treatment for superficial bladder cancer?

Why does this work?

A

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)

28
Q

Four promising immunotherapies against tumor cells

A
  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.
29
Q

5 Methods used for tumor vaccines

A
  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
30
Q

therapeutic cancer vaccine for prostate cancer

A

Sipuleucel-T

.Patient’s blood –> DC’s + fusion protein consisting of the antigen prostatic acid phosphatase (PAP) and GM-CSF

31
Q

Monoclonal antibodies for cancer therapy (4)

A

Rituxan = Anti-CD20 (targets B cells)

Herceptin = Anti-EFG-receptor-2 (a.k.a. HER2)

Erbitux = anti-EGFR (HER1)

Avastin = blocks VEGF receptor

32
Q

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

A

OncoScint, ProstaScint

33
Q

Immunization with MAGE-1/3 induces…

A

anti-melanoma immune response

34
Q

Rituximab target

A

CD20

35
Q

Traztuzumab target

A

HER2

36
Q

Alemtuzumab target

A

CD52

37
Q

Cetruximab target

A

EGFR

38
Q

Panitumumab target

A

EGFR

39
Q

Bevacizumab

A

VEGF

40
Q

Gemtuzumab target

A

CD33

41
Q

Ibritumomab and Tositumomab target

A

CD20

42
Q

Monoclonal antibodies to tumor antigens can deliver _____or ____ to tumor cells

A

Toxins or NK cells